Artykuły w czasopismach na temat „Neuroprotective proteins”
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Zhang, Jianmin, Jia Yang, Huaishan Wang, Omar Sherbini, Matthew J. Keuss, George KE Umanah, Emily Ling-Lin Pai i in. "The AAA + ATPase Thorase is neuroprotective against ischemic injury". Journal of Cerebral Blood Flow & Metabolism 39, nr 9 (16.04.2018): 1836–48. http://dx.doi.org/10.1177/0271678x18769770.
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Neuronal preconditioning in vitro or in vivo with a stressful but non-lethal stimulus leads to new protein expression that mediates a profound neuroprotection against glutamate excitotoxicity and experimental stroke. The proteins that mediate neuroprotection are relatively unknown and under discovery. Here we find that the expression of the AAA + ATPase Thorase is induced by preconditioning stimulation both in vitro and in vivo. Thorase provides neuroprotection in an ATP-dependent manner against oxygen–glucose deprivation (OGD) neurotoxicity or glutamate N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in vitro. Knock-down of Thorase prevents the establishment of preconditioning induced neuroprotection against OGD or NMDA neurotoxicity. Transgenic overexpression of Thorase provides neuroprotection in vivo against middle cerebral artery occlusion (MCAO)-induced stroke in mice, while genetic deletion of Thorase results in increased injury in vivo following stroke. These results define Thorase as a neuroprotective protein and understanding Thorase signaling could offer a new therapeutic strategy for the treatment of neurologic disorders.
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Puchowicz, Michelle A., Jennifer L. Zechel, Jose Valerio, Douglas S. Emancipator, Kui Xu, Svetlana Pundik, Joseph C. LaManna i W. David Lust. "Neuroprotection in Diet-Induced Ketotic Rat Brain after Focal Ischemia". Journal of Cerebral Blood Flow & Metabolism 28, nr 12 (23.07.2008): 1907–16. http://dx.doi.org/10.1038/jcbfm.2008.79.
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Neuroprotective properties of ketosis may be related to the upregulation of hypoxia inducible factor (HIF)-1α, a primary constituent associated with hypoxic angiogenesis and a regulator of neuroprotective responses. The rationale that the utilization of ketones by the brain results in elevation of intracellular succinate, a known inhibitor of prolyl hydroxylase (the enzyme responsible for the degradation of HIF-1α) was deemed as a potential mechanism of ketosis on the upregulation of HIF-1α. The neuroprotective effect of diet-induced ketosis (3 weeks of feeding a ketogenic diet), as pretreatment, on infarct volume, after reversible middle cerebral artery occlusion (MCAO), and the upregulation of HIF-1α were investigated. The effect of β-hydroxybutyrate (BHB), as a pretreatment, via intraventricular infusion (4 days of infusion before stroke) was also investigated following MCAO. Levels of HIF-1α and Bcl-2 (anti-apoptotic protein) proteins and succinate content were measured. A 55% or 70% reduction in infarct volume was observed with BHB infusion or diet-induced ketosis, respectively. The levels of HIF-1α and Bcl-2 proteins increased threefold with diet-induced ketosis; BHB infusions also resulted in increases in these proteins. As hypothesized, succinate content increased by 55% with diet-induced ketosis and fourfold with BHB infusion. In conclusion, the biochemical link between ketosis and the stabilization of HIF-1α is through the elevation of succinate, and both HIF-1α stabilization and Bcl-2 upregulation play a role in ketone-induced neuroprotection in the brain.
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Shen, Shichen, Ming Zhang, Min Ma, Sailee Rasam, David Poulsen i Jun Qu. "Potential Neuroprotective Mechanisms of Methamphetamine Treatment in Traumatic Brain Injury Defined by Large-Scale IonStar-Based Quantitative Proteomics". International Journal of Molecular Sciences 22, nr 5 (24.02.2021): 2246. http://dx.doi.org/10.3390/ijms22052246.
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Although traumatic brain injury (TBI) causes hospitalizations and mortality worldwide, there are no approved neuroprotective treatments, partly due to a poor understanding of the molecular mechanisms underlying TBI neuropathology and neuroprotection. We previously reported that the administration of low-dose methamphetamine (MA) induced significant functional/cognitive improvements following severe TBI in rats. We further demonstrated that MA mediates neuroprotection in part, via dopamine-dependent activation of the PI3K-AKT pathway. Here, we further investigated the proteomic changes within the rat cortex and hippocampus following mild TBI (TM), severe TBI (TS), or severe TBI plus MA treatment (TSm) compared to sham operated controls. We identified 402 and 801 altered proteins (APs) with high confidence in cortical and hippocampal tissues, respectively. The overall profile of APs observed in TSm rats more closely resembled those seen in TM rather than TS rats. Pathway analysis suggested beneficial roles for acute signaling through IL-6, TGFβ, and IL-1β. Moreover, changes in fibrinogen levels observed in TSm rats suggested a potential role for these proteins in reducing/preventing TBI-induced coagulopathies. These data facilitate further investigations to identify specific pathways and proteins that may serve as key targets for the development of neuroprotective therapies.
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Chan, Elaine W. L., Emilia T. Y. Yeo, Kelly W. L. Wong, Mun L. See, Ka Y. Wong, Jeremy K. Y. Yap i Sook Y. Gan. "Piper sarmentosum Roxb. Attenuates Beta Amyloid (Aβ)-Induced Neurotoxicity Via the Inhibition of Amyloidogenesis and Tau Hyperphosphorylation in SH-SY5Y Cells". Current Alzheimer Research 18, nr 1 (28.04.2021): 80–87. http://dx.doi.org/10.2174/1567205018666210324124239.
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Background: In Alzheimer’s disease, accumulation of beta amyloid (Aβ) triggers amyloidogenesis and hyperphosphorylation of tau protein leading to neuronal cell death. Piper sarmentosum Roxb. (PS) is a traditional medicinal herb used by Malay to treat rheumatism, headache and boost memory. It possesses various biological effects, such as anti-cholinergic, anti-inflammatory, anti-oxidant and anti-depressant-like effects. Objective: The present study aimed to investigate neuroprotective properties of PS against Aβ-induced neurotoxicity and to evaluate its potential mechanism of action. Methods: Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against Aβ-induced neurotoxicity were investigated in SH-SY5Y human neuroblastoma cells. Cells were pre-treated with PS for 24 h followed by 24 h of induction with Aβ. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular Aβ and tau proteins phosphorylated at threonine 231 (pT231) were determined. Gene and protein expressions were assessed using qRT-PCR analyses and western blot analyses, respectively. Results: Hexane extracts of PS (LHXN and RHXN) protected SH-SY5Y cells against Aβ-induced neurotoxicity, and decreased levels of extracellular Aβ and phosphorylated tau (pT231). Although extracts of PS inhibited Aβ-induced ROS production, it was unlikely that neuroprotective effects were simply due to the anti-oxidant capacity of PS. Further, mechanistic study suggested that the neuroprotective effects of PS might be due to its capability to regulate amyloidogenesis through the downregulation of BACE and APP. Conclusion: These findings suggest that hexane extracts of PS confer neuroprotection against Aβ- induced neurotoxicity in SH-SY5Y cells by attenuating amyloidogenesis and tau hyperphosphorylation. Due to its neuroprotective properties, PS might be a potential therapeutic agent for Alzheimer’s disease.
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Kim, Jong Youl, Sumit Barua, Mei Ying Huang, Joohyun Park, Midori A. Yenari i Jong Eun Lee. "Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury". Cells 9, nr 9 (2.09.2020): 2020. http://dx.doi.org/10.3390/cells9092020.
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The 70 kDa heat shock protein (HSP70) is a stress-inducible protein that has been shown to protect the brain from various nervous system injuries. It allows cells to withstand potentially lethal insults through its chaperone functions. Its chaperone properties can assist in protein folding and prevent protein aggregation following several of these insults. Although its neuroprotective properties have been largely attributed to its chaperone functions, HSP70 may interact directly with proteins involved in cell death and inflammatory pathways following injury. Through the use of mutant animal models, gene transfer, or heat stress, a number of studies have now reported positive outcomes of HSP70 induction. However, these approaches are not practical for clinical translation. Thus, pharmaceutical compounds that can induce HSP70, mostly by inhibiting HSP90, have been investigated as potential therapies to mitigate neurological disease and lead to neuroprotection. This review summarizes the neuroprotective mechanisms of HSP70 and discusses potential ways in which this endogenous therapeutic molecule could be practically induced by pharmacological means to ultimately improve neurological outcomes in acute neurological disease.
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Hawkins, Liam J., Hanane Hadj-Moussa, Vu C. Nguyen, Matthew E. Pamenter i Kenneth B. Storey. "Naked mole rats activate neuroprotective proteins during hypoxia". Journal of Experimental Zoology Part A: Ecological and Integrative Physiology 331, nr 10 (23.09.2019): 571–76. http://dx.doi.org/10.1002/jez.2321.
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Gozes, Illana. "The cytoskeleton as a drug target for neuroprotection: the case of the autism- mutated ADNP". Biological Chemistry 397, nr 3 (1.03.2016): 177–84. http://dx.doi.org/10.1515/hsz-2015-0152.
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Abstract Fifteen years ago we discovered activity-dependent neuroprotective protein (ADNP), and showed that it is essential for brain formation/function. Our protein interaction studies identified ADNP as a member of the chromatin remodeling complex, SWI/SNF also associated with alternative splicing of tau and prediction of tauopathy. Recently, we have identified cytoplasmic ADNP interactions with the autophagy regulating microtubule-associated protein 1 light chain 3 (LC3) and with microtubule end-binding (EB) proteins. The ADNP-EB-binding SIP domain is shared with the ADNP snippet drug candidate, NAPVSIPQ termed NAP (davunetide). Thus, we identified a precise target for ADNP/NAP (davunetide) neuroprotection toward improved drug development.
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Bayliss, Jacqueline A., i Zane B. Andrews. "Ghrelin is neuroprotective in Parkinson’s disease: molecular mechanisms of metabolic neuroprotection". Therapeutic Advances in Endocrinology and Metabolism 4, nr 1 (luty 2013): 25–36. http://dx.doi.org/10.1177/2042018813479645.
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Ghrelin is a circulating orexigenic signal that rises with prolonged fasting and falls postprandially. Ghrelin regulates energy homeostasis by stimulating appetite and body weight; however, it also has many nonmetabolic functions including enhanced learning and memory, anxiolytic effects as well as being neuroprotective. In Parkinson’s disease, ghrelin enhances dopaminergic survival via reduced microglial and caspase activation and improved mitochondrial function. As mitochondrial dysfunction contributes to Parkinson’s disease, any agent that enhances mitochondrial function could be a potential therapeutic target. We propose that ghrelin provides neuroprotective effects via AMPK (5′ adenosine monophosphate-activated protein kinase) activation and enhanced mitophagy (removal of damaged mitochondria) to ultimately enhance mitochondrial bioenergetics. AMPK activation shifts energy balance from a negative to a neutral state and has a role in regulating mitochondrial biogenesis and reducing reactive oxygen species production. Mitophagy is important in Parkinson’s disease because damaged mitochondria produce reactive oxygen species resulting in damage to intracellular proteins, lipids and DNA predisposing them to neurodegeneration. Many genetic mutations linked to Parkinson’s disease are due to abnormal mitochondrial function and mitophagy, for example LRRK2, PINK1 and Parkin. An interaction between ghrelin and these classic Parkinson’s disease markers has not been observed, however by enhancing mitochondrial function, ghrelin or AMPK is a potential therapeutic target for slowing the progression of Parkinson’s disease symptoms, both motor and nonmotor.
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Logsdon, Aric F., Michelle A. Erickson, Xiaodi Chen, Joseph Qiu, Yow-Pin Lim, Barbara S. Stonestreet i William A. Banks. "Inter-alpha inhibitor proteins attenuate lipopolysaccharide-induced blood–brain barrier disruption and downregulate circulating interleukin 6 in mice". Journal of Cerebral Blood Flow & Metabolism 40, nr 5 (24.06.2019): 1090–102. http://dx.doi.org/10.1177/0271678x19859465.
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Circulating levels of inter-alpha inhibitor proteins change dramatically in acute inflammatory disorders, which suggest an important contribution to the immunomodulatory system. Human blood-derived inter-alpha inhibitor proteins are neuroprotective and improve survival of neonatal mice exposed to lipopolysaccharide. Lipopolysaccharide augments inflammatory conditions and disrupts the blood–brain barrier. There is a paucity of therapeutic strategies to treat blood–brain barrier dysfunction, and the neuroprotective effects of human blood-derived inter-alpha inhibitor proteins are not fully understood. To examine the therapeutic potential of inter-alpha inhibitor proteins, we administered human blood-derived inter-alpha inhibitor proteins to male and female CD-1 mice after lipopolysaccharide exposure and quantified blood–brain barrier permeability of intravenously injected14C-sucrose and99mTc-albumin. We hypothesized that human blood-derived inter-alpha inhibitor protein treatment would attenuate lipopolysaccharide-induced blood–brain barrier disruption and associated inflammation. Lipopolysaccharide increased blood–brain barrier permeability to both14C-sucrose and99mTc-albumin, but human blood-derived inter-alpha inhibitor protein treatment only attenuated increases in14C-sucrose blood–brain barrier permeability in male mice. Lipopolysaccharide stimulated a more robust elevation of male serum inter-alpha inhibitor protein concentration compared to the elevation measured in female serum. Lipopolysaccharide administration also increased multiple inflammatory factors in serum and brain tissue, including interleukin 6. Human blood-derived inter-alpha inhibitor protein treatment downregulated serum interleukin 6 levels, which were inversely correlated with serum inter-alpha inhibitor protein concentration. We conclude that inter-alpha inhibitor proteins may be neuroprotective through mechanisms of blood–brain barrier disruption associated with systemic inflammation.
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Snider, B. Joy. "Neuroprotective Mechanisms of Heat Shock Gene Expression". Neuroscientist 4, nr 4 (lipiec 1998): 236–39. http://dx.doi.org/10.1177/107385849800400412.
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Heat shock proteins were initially described as the predominant proteins expressed immediately after a thermal stress. These ubiquitously expressed proteins function as molecular chaperones; they aid in the folding, subcellular translocation, and assembly of other proteins. Although most of these proteins are expressed constitutively, enhanced expression, induced by stress or genetic manipulations, can reduce subsequent cellular injury in many cell types, including neurons and glia. Further understanding of how the expression of these proteins is controlled in the nervous system, and how they can be manipulated to attenuate injury, could provide therapeutic targets for cerebral ischemia and neurodegenerative disorders.
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Duan, Yunxia, Di Wu, Mitchell Huber, Jingfei Shi, Hong An, Wenjing Wei, Xiaoduo He, Yuchuan Ding i Xunming Ji. "New Endovascular Approach for Hypothermia With Intrajugular Cooling and Neuroprotective Effect in Ischemic Stroke". Stroke 51, nr 2 (luty 2020): 628–36. http://dx.doi.org/10.1161/strokeaha.119.026523.
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Background and Purpose— Induction of hypothermia as a stroke therapy has been limited by logistical challenges. This study was designed to determine the hypothermic and neuroprotective efficacy of infusing cold saline directly into the internal jugular (IJ) vein and compare the effects of IJ hypothermia to those achieved by intracarotid artery hypothermia in an ischemic stroke model. Methods— The right middle cerebral artery was occluded in rats using an intraluminal filament. Immediately following reperfusion, hypothermia was achieved by infusing isotonic saline through microcatheter into the right IJ or right intracarotid over 30 minutes. Infarct sizes, neurological deficits, blood-brain barrier damage, edema volume, blood-brain barrier associated molecules (MMP-9 [matrix metallopeptidase 9] and AQP-4 [aquaporin 4]), and apoptosis-associated proteins (Bcl-2 and cleaved Caspase-3) were measured. Results— We found that both IJ- and intracarotid-based infusion cooled the brain robustly with a minimal effect on rectal temperatures. This brain cooling led to significantly reduced infarct volumes at 24 hours after reperfusion, as well as decreased expression of the proapoptotic protein cleaved Caspase-3 and increased expression of the antiapoptotic protein Bcl-2. Intracarotid and IJ cooling also aided in blood-brain barrier maintenance, as shown by decreased edema volumes, reduced Evans Blue leakage, and decreased expression of edema-facilitating proteins (MMP-9 and AQP-4). Both cooling methods then translated to preserved neurological function as determined by multiple functional tests over a 28-day observation period. Most importantly, the cooling and neuroprotective efficacy of IJ cooling was comparable to intracarotid cooling by almost every metric evaluated. Conclusions— Compared with intracarotid infusion, IJ infusion conferred a similar degree of hypothermia and neuroprotection following ischemic stroke. Given the ease of establishing vascular access via the internal jugular vein and the powerful neuroprotection that hypothermia provides, IJ brain cooling could be used as a promising hypothermia-induction modality going forward.
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Liu, Hui, Golam T. Saffi, Maryam S. Vasefi, Youngjik Choi, Jeff S. Kruk, Nawaz Ahmed, Nyasha Gondora, John Mielke, Zoya Leonenko i Michael A. Beazely. "Amyloid-β Inhibits PDGFβ Receptor Activation and Prevents PDGF-BBInduced Neuroprotection". Current Alzheimer Research 15, nr 7 (9.05.2018): 618–27. http://dx.doi.org/10.2174/1567205015666180110110321.
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Background: PDGFβ receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins. Objective: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD). Methods and Results: In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid-β treatment for 24 h decreased surviving cell number in a concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any neuroprotection against amyloid-β in primary neurons and only very limited protective effects in SH-SY5Y cells. In addition to its neuroprotective action, PDGF promotes cell growth and division in several systems, and the application of PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell number. Amyloid-β attenuated the mitogenic effects of PDGF-BB, inhibited PDGF-BB-induced PDGFβ receptor phosphorylation, and attenuated the ability of PDGF-BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of amyloid-β to inhibit PDGFβ receptor activation, immunoprecipitation experiments failed to detect a physical interaction between amyloid-β and PDGF-BB or the PDGFβ receptor. However, G protein-coupled receptor transactivation of the PDGFβ receptor (an exclusively intracellular signaling pathway) remained unaffected by the presence of amyloid-β. Conclusions: As the PDGF system is upregulated upon neuronal damage, the ability of amyloid-β to inhibit this endogenous neuroprotective system should be further investigated in the context of AD pathophysiology.
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Lin, En-Ju D., C. Wymond Symes, Andrea Townsend-Nicholson, Matthias Klugmann, Claudia B. Klugmann, Klaus Lehnert, Dahna Fong, Deborah Young i Matthew J. During. "An Immunological Approach to Increase the Brain’s Resilience to Insults". ISRN Neuroscience 2014 (24.04.2014): 1–10. http://dx.doi.org/10.1155/2014/103213.
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We have previously demonstrated the therapeutic potential of inducing a humoral response with autoantibodies to the N-methyl D-aspartate (NMDA) receptor using a genetic approach. In this study, we generated three recombinant proteins to different functional domains of the NMDA receptor, which is implicated in mediating brain tolerance, specifically NR1[21–375], NR1[313–619], NR1[654–800], and an intracellular scaffolding protein, Homer1a, with a similar anatomical expression pattern. All peptides showed similar antigenicity and antibody titers following systemic vaccination, and all animals thrived. Two months following vaccination, rats were administered the potent neurotoxin, kainic acid. NR1[21–375] animals showed an antiepileptic phenotype but no neuroprotection. Remarkably, despite ineffective antiepileptic activity, 6 of 7 seizing NR1[654–800] rats showed absolutely no injury with only minimal changes in the remaining animal, whereas the majority of persistently seizing rats in the other groups showed moderate to severe hippocampal injury. CREB, BDNF, and HSP70, proteins associated with preconditioning, were selectively upregulated in the hippocampus of NR1[654–800] animals, consistent with the observed neuroprotective phenotype. These results identify NR1 epitopes important in conferring anticonvulsive and neuroprotective effects and support the concept of an immunological strategy to induce a chronic state of tolerance in the brain.
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Xu, Jia, Fang Wang, Jiejie Guo, Chunshuang Xu, Yanzi Cao, Zhiling Fang i Qinwen Wang. "Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer’s Disease". International Journal of Molecular Sciences 21, nr 6 (18.03.2020): 2071. http://dx.doi.org/10.3390/ijms21062071.
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Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer’s disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein–protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.
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Shimada, Tadayuki, Alyson E. Fournier i Kanato Yamagata. "Neuroprotective Function of 14-3-3 Proteins in Neurodegeneration". BioMed Research International 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/564534.
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14-3-3 proteins are abundantly expressed adaptor proteins that interact with a vast number of binding partners to regulate their cellular localization and function. They regulate substrate function in a number of ways including protection from dephosphorylation, regulation of enzyme activity, formation of ternary complexes and sequestration. The diversity of 14-3-3 interacting partners thus enables 14-3-3 proteins to impact a wide variety of cellular and physiological processes. 14-3-3 proteins are broadly expressed in the brain, and clinical and experimental studies have implicated 14-3-3 proteins in neurodegenerative disease. A recurring theme is that 14-3-3 proteins play important roles in pathogenesis through regulating the subcellular localization of target proteins. Here, we review the evidence that 14-3-3 proteins regulate aspects of neurodegenerative disease with a focus on their protective roles against neurodegeneration.
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Rocha, Nicole Kemberly Ribeiro, Vanessa De Jesus Rodrigues de Paula, Orestes V. Forlenza, Daniel S. Kerr i Helena Brentani. "Influence of lithium in neuron-glia interaction in hippocampal neurons". Revista de Medicina 97, nr 6 (30.12.2018): 533–46. http://dx.doi.org/10.11606/issn.1679-9836.v97i6p533-546.
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Recently, special attention has been given to the possible neuroprotective effects of lithium, especially by the discovery of its regulatory effects on pro and anti-apoptotic proteins. Lithium substantially increases the cytoprotective proteins expression in the central nervous system, both in rat cortex and in human cells of neuronal origin. In addition to neuroprotective actions, it aids in the regeneration of axons in the central nervous system of mammals. Lithium negatively regulates the expression and activity of enzymes that exert important functions in cerebral homeostasis: synaptic plasticity, neurogenesis, and phosphorylation of tau protein. Microglia is known for its importance in neuropathology. However, under physiological conditions, such immune cells interact actively with neurons, being able to modulate the fate and functions of the synapses. Such ability of microglial cells suggests the consequences of changes in microglial phenotype under pathological conditions, which makes it relevant to understand the interaction between microglial and other developing brain cells and their influence on the formation of neuronal and synaptic networks. The current work aims to identify the main pathway of neuronal-glia integration activated by chronic treatment with lithium in neurons, exploring the use of bioinformatics tools in microarray data. Treatment of primary hippocampal neurons with lithium changed the genes related to different neuroprotection pathways at the highest therapeutic dose. There was dissociation between the therapeutic and sub-therapeutic dose of lithium in neuroprotection. Therefore, treatment at therapeutic doses (2mM) modified different signaling pathways when compared to the sub-therapeutic dose (0.02 and 0.2mM).
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Dobolyi, Arpád, Csilla Vincze, Gabriella Pál i Gábor Lovas. "The Neuroprotective Functions of Transforming Growth Factor Beta Proteins". International Journal of Molecular Sciences 13, nr 7 (3.07.2012): 8219–58. http://dx.doi.org/10.3390/ijms13078219.
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Hoffer, B., M. Airavaara i M. H. Voutilainen. "2.14.1 NEUROPROTECTIVE AND NEUROREGENERATIVE TROPHIC PROTEINS IN PARKINSON'S DISEASE". Parkinsonism & Related Disorders 18 (styczeń 2012): S87. http://dx.doi.org/10.1016/s1353-8020(11)70420-5.
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Chung, Yin-Sir, Pervaiz Khalid Ahmed, Iekhsan Othman i Mohd Farooq Shaikh. "Orthosiphon stamineus Proteins Alleviate Hydrogen Peroxide Stress in SH-SY5Y Cells". Life 11, nr 6 (20.06.2021): 585. http://dx.doi.org/10.3390/life11060585.
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The neuroprotective potential of Orthosiphon stamineus leaf proteins (OSLPs) has never been evaluated in SH-SY5Y cells challenged by hydrogen peroxide (H2O2). This work thus aims to elucidate OSLP neuroprotective potential in alleviating H2O2 stress. OSLPs at varying concentrations were evaluated for cytotoxicity (24 and 48 h) and neuroprotective potential in H2O2-induced SH-SY5Y cells (24 h). The protective mechanism of H2O2-induced SH-SY5Y cells was also explored via mass-spectrometry-based label-free quantitative proteomics (LFQ) and bioinformatics. OSLPs (25, 50, 125, 250, 500, and 1000 µg/mL; 24 and 48 h) were found to be safe. Pre-treatments with OSLP doses (250, 500, and 1000 µg/mL, 24 h) significantly increased the survival of SH-SY5Y cells in a concentration-dependent manner and improved cell architecture—pyramidal-shaped cells, reduced clumping and shrinkage, with apparent neurite formations. OSLP pre-treatment (1000 µg/mL, 24 h) lowered the expressions of two major heat shock proteins, HSPA8 (heat shock protein family A (Hsp70) member 8) and HSP90AA1 (heat shock protein 90), which promote cellular stress signaling under stress conditions. OSLP is, therefore, suggested to be anti-inflammatory by modulating the “signaling of interleukin-4 and interleukin-13” pathway as the predominant mechanism in addition to regulating the “attenuation phase” and “HSP90 chaperone cycle for steroid hormone receptors” pathways to counteract heat shock protein (HSP)-induced damage under stress conditions.
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Gil, Antonio, Elisa Martín-Montañez, Nadia Valverde, Estrella Lara, Federica Boraldi, Silvia Claros, Silvana-Yanina Romero-Zerbo, Oscar Fernández, Jose Pavia i Maria Garcia-Fernandez. "Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage". Cells 10, nr 1 (29.12.2020): 34. http://dx.doi.org/10.3390/cells10010034.
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Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.
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Furukawa, Katsutoshi, Steven Estus, Weiming Fu, Robert J. Mark i Mark P. Mattson. "Neuroprotective Action of Cycloheximide Involves Induction of Bcl-2 and Antioxidant Pathways". Journal of Cell Biology 136, nr 5 (10.03.1997): 1137–49. http://dx.doi.org/10.1083/jcb.136.5.1137.
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The ability of the protein synthesis inhibitor cycloheximide (CHX) to prevent neuronal death in different paradigms has been interpreted to indicate that the cell death process requires synthesis of “killer” proteins. On the other hand, data indicate that neurotrophic factors protect neurons in the same death paradigms by inducing expression of neuroprotective gene products. We now provide evidence that in embryonic rat hippocampal cell cultures, CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including the antiapoptotic gene bcl-2 and antioxidant enzymes. Neuronal survival after exposure to glutamate, FeSO4, and amyloid β-peptide was increased in cultures pretreated with CHX at concentrations of 50–500 nM; higher and lower concentrations were ineffective. Neuroprotective concentrations of CHX caused only a moderate (20–40%) reduction in overall protein synthesis, and induced an increase in c-fos, c-jun, and bcl-2 mRNAs and protein levels as determined by reverse transcription–PCR analysis and immunocytochemistry, respectively. At neuroprotective CHX concentrations, levels of c-fos heteronuclear RNA increased in parallel with c-fos mRNA, indicating that CHX acts by inducing transcription. Neuroprotective concentrations of CHX suppressed accumulation of H2O2 induced by FeSO4, suggesting activation of antioxidant pathways. Treatment of cultures with an antisense oligodeoxynucleotide directed against bcl-2 mRNA decreased Bcl-2 protein levels and significantly reduced the neuroprotective action of CHX, suggesting that induction of Bcl-2 expression was mechanistically involved in the neuroprotective actions of CHX. In addition, activity levels of the antioxidant enzymes Cu/ Zn-superoxide dismutase, Mn-superoxide dismutase, and catalase were significantly increased in cultures exposed to neuroprotective levels of CHX. Our data suggest that low concentrations of CHX can promote neuron survival by inducing increased levels of gene products that function in antioxidant pathways, a neuroprotective mechanism similar to that used by neurotrophic factors.
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Tirapelli, Daniela Pretti da Cunha, Carlos Gilberto Carlotti Junior, João Pereira Leite, Luis Fernando Tirapelli i Benedicto Oscar Colli. "Expression of HSP70 in cerebral ischemia and neuroprotetive action of hypothermia and ketoprofen". Arquivos de Neuro-Psiquiatria 68, nr 4 (sierpień 2010): 592–96. http://dx.doi.org/10.1590/s0004-282x2010000400021.
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Heat shock proteins (HSPs) are molecular chaperones that bind to other proteins to shepherd them across membranes and direct them to specific locations within a cell. Several injurious stimuli can induce Hsp70 expression, including ischemia. This study aimed to investigate the pattern of expression of protein (immunohistochemistry) and gene (real-time PCR) Hsp70 in experimental focal cerebral ischemia in rats by occlusion of the middle cerebral artery for 1 hour and the role of neuroprotection with hypothermia (H) and ketoprofen (K). The infarct volume was measured using morphometric analysis defined by triphenyl tetrazolium chloride. It was observed increases in the protein (p=0.0001) and gene (p=0.0001) Hsp70 receptor in the ischemic areas that were reduced by H (protein and gene: p<0.05), K (protein: p<0.001), and H+K (protein: p<0.01 and gene: p<0.05). The Hsp70 increases in the ischemic area suggests that the Hsp70-mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, H and K are directly involved with the Hsp70.
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Nakka, Venkata P., Bradley T. Lang, Deborah J. Lenschow, Dong-Er Zhang, Robert J. Dempsey i Raghu Vemuganti. "Increased Cerebral Protein ISGylation after Focal Ischemia is Neuroprotective". Journal of Cerebral Blood Flow & Metabolism 31, nr 12 (17.08.2011): 2375–84. http://dx.doi.org/10.1038/jcbfm.2011.103.
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Addition of a small peptide called ISG15 is known as ISGylation, which is an ubiquitin (ub)-like posttranslational modification. We currently show that focal ischemia induced by transient middle cerebral artery occlusion (MCAO) in adult mice significantly induces cortical protein ISGylation between 6 and 24 hours reperfusion. With two-dimensional western blotting, 45 proteins were observed to be significantly increased in ISGylation (by 1.8- to 9.7-fold) after focal ischemia compared with sham control. Immunochemistry showed that ISGylated proteins are localized in neurons within the ipsilateral striatum and in astroglia within the peri-infarct cortex of ischemic mice. When subjected to transient MCAO, ISG15−/− mice showed increased mortality, exacerbated infarction, and worsened neurologic recovery than did wild-type controls. In addition, mice lacking UBE1L (ub-activating enzyme E1-like protein, the first enzyme of the ISGylation cycle) also showed bigger infarcts when subjected to transient MCAO. Regional cerebral blood flow or other physiologic parameters were not significantly different in both knockouts compared with wild-type controls. These studies indicate that increased protein ISGylation might be an endogenous neuroprotective adaptation to minimize poststroke brain damage.
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Bordet, R., T. Ouk, O. Petrault, P. Gelé, S. Gautier, M. Laprais, D. Deplanque i in. "PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases". Biochemical Society Transactions 34, nr 6 (25.10.2006): 1341–46. http://dx.doi.org/10.1042/bst0341341.
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PPARs (peroxisome-proliferator-activated receptors) are ligand-activated transcriptional factor receptors belonging to the so-called nuclear receptor family. The three isoforms of PPAR (α, β/δ and γ) are involved in regulation of lipid or glucose metabolism. Beyond metabolic effects, PPARα and PPARγ activation also induces anti-inflammatory and antioxidant effects in different organs. These pleiotropic effects explain why PPARα or PPARγ activation has been tested as a neuroprotective agent in cerebral ischaemia. Fibrates and other non-fibrate PPARα activators as well as thiazolidinediones and other non-thiazolidinedione PPARγ agonists have been demonstrated to induce both preventive and acute neuroprotection. This neuroprotective effect involves both cerebral and vascular mechanisms. PPAR activation induces a decrease in neuronal death by prevention of oxidative or inflammatory mechanisms implicated in cerebral injury. PPARα activation induces also a vascular protection as demonstrated by prevention of post-ischaemic endothelial dysfunction. These vascular effects result from a decrease in oxidative stress and prevention of adhesion proteins, such as vascular cell adhesion molecule 1 or intercellular cell-adhesion molecule 1. Moreover, PPAR activation might be able to induce neurorepair and endothelium regeneration. Beyond neuroprotection in cerebral ischaemia, PPARs are also pertinent pharmacological targets to induce neuroprotection in chronic neurodegenerative diseases.
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Mu, Lirong, Chaojie Hui i Wenhui Li. "Morin Provides Neuroprotection in a Model of Cerebral Infarction Via Nrf-2 Signaling Pathway". Current Topics in Nutraceutical Research 19, nr 4 (19.02.2021): 438–44. http://dx.doi.org/10.37290/ctnr2641-452x.19:438-444.
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Cerebral infarction, also known as ischemic stroke, is a disorder of blood supply in the local brain tissue and the second leading cause of death worldwide. It is important to develop effective drugs to treat cerebral infarction. Morin (3,5,7,2′, 4′-pentahydroxyflavone) is a bioactive flavonol that has multiple medicinal properties including antioxidant, anti-inflammatory, anti-invasive, antitumor, and antiangiogenic properties. However, its potential effect on ischemic stroke as a potent neuroprotective and cardioprotective agent remains unknown. In this study, we constructed a rat model of cerebral infarction and shown morin to be neuroprotective in this model. Additionally, morin inhibited nerve cell apoptosis and cerebral infarction induced oxidative stress in brain tissue. Our data further confirmed that morin provides neuroprotection in cerebral infarction via upregulation of the downstream proteins of Nrf2 pathway. We therefore suggest morin as a promising therapeutic drug for the treatment of cerebral infarction.
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Pazdernik, T. L., M. R. Emerson, R. Cross, S. R. Nelson i F. E. Samson. "Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins". Journal of Applied Toxicology 21, S1 (grudzień 2001): S87—S94. http://dx.doi.org/10.1002/jat.818.
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Romero, Juan Ignacio, Mariana Inés Holubiec, Tamara Logica Tornatore, Stéphanie Rivière, Eva-Maria Hanschmann, Rodolfo Alberto Kölliker-Frers, Julia Tau i in. "Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration". Oxidative Medicine and Cellular Longevity 2017 (2017): 1–14. http://dx.doi.org/10.1155/2017/4162465.
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The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.
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Zhu, Yi, Chong Li, Xianzun Tao, Jennifer M. Brazill, Joun Park, Zoraida Diaz-Perez i R. Grace Zhai. "Nmnat restores neuronal integrity by neutralizing mutant Huntingtin aggregate-induced progressive toxicity". Proceedings of the National Academy of Sciences 116, nr 38 (4.09.2019): 19165–75. http://dx.doi.org/10.1073/pnas.1904563116.
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Accumulative aggregation of mutant Huntingtin (Htt) is a primary neuropathological hallmark of Huntington’s disease (HD). Currently, mechanistic understanding of the cytotoxicity of mutant Htt aggregates remains limited, and neuroprotective strategies combating mutant Htt-induced neurodegeneration are lacking. Here, we show that in Drosophila models of HD, neuronal compartment-specific accumulation of mutant Htt aggregates causes neurodegenerative phenotypes. In addition to the increase in the number and size, we discovered an age-dependent acquisition of thioflavin S+, amyloid-like adhesive properties of mutant Htt aggregates and a concomitant progressive clustering of aggregates with mitochondria and synaptic proteins, indicating that the amyloid-like adhesive property underlies the neurotoxicity of mutant Htt aggregation. Importantly, nicotinamide mononucleotide adenylyltransferase (NMNAT), an evolutionarily conserved nicotinamide adenine dinucleotide (NAD+) synthase and neuroprotective factor, significantly mitigates mutant Htt-induced neurodegeneration by reducing mutant Htt aggregation through promoting autophagic clearance. Additionally, Nmnat overexpression reduces progressive accumulation of amyloid-like Htt aggregates, neutralizes adhesiveness, and inhibits the clustering of mutant Htt with mitochondria and synaptic proteins, thereby restoring neuronal function. Conversely, partial loss of endogenous Nmnat exacerbates mutant Htt-induced neurodegeneration through enhancing mutant Htt aggregation and adhesive property. Finally, conditional expression of Nmnat after the onset of degenerative phenotypes significantly delays the progression of neurodegeneration, revealing the therapeutic potential of Nmnat-mediated neuroprotection at advanced stages of HD. Our study uncovers essential mechanistic insights to the neurotoxicity of mutant Htt aggregation and describes the molecular basis of Nmnat-mediated neuroprotection in HD.
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Chen, I.-Cheng, Chia-Ning Chang, Wan-Ling Chen, Te-Hsien Lin, Chih-Ying Chao, Chih-Hsin Lin, Hsuan-Yuan Lin i in. "Targeting Ubiquitin Proteasome Pathway with Traditional Chinese Medicine for Treatment of Spinocerebellar Ataxia Type 3". American Journal of Chinese Medicine 47, nr 01 (styczeń 2019): 63–95. http://dx.doi.org/10.1142/s0192415x19500046.
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Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q[Formula: see text]-GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q[Formula: see text]-GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q[Formula: see text]-GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q[Formula: see text]-GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders.
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Peng, Zhanglong, Supinder Bedi, Vivek Mann, Alamelu Sundaresan, Kohei Homma, Gregory Gaskey, Minoru Kowada i in. "Neuroprotective Effects of Asparagus officinalis Stem Extract in Transgenic Mice Overexpressing Amyloid Precursor Protein". Journal of Immunology Research 2021 (10.05.2021): 1–10. http://dx.doi.org/10.1155/2021/8121407.
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To mimic Alzheimer’s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.
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Gavín, Rosalina, Laia Lidón, Isidre Ferrer i José Antonio del Río. "The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain". Cells 9, nr 3 (2.03.2020): 591. http://dx.doi.org/10.3390/cells9030591.
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Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
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Prandini, Mirto N., Antonio Neves Filho, Antonio J. Lapa i João N. Stavale. "Mild hypothermia reduces polymorphonuclear leukocytes infiltration in induced brain inflammation". Arquivos de Neuro-Psiquiatria 63, nr 3b (wrzesień 2005): 779–84. http://dx.doi.org/10.1590/s0004-282x2005000500012.
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Over the last 50 years deep hypothermia (23(0) C) has demonstrated to be an excellent neuroprotective agent in cerebral ischemic injury. Mild hypothermia (31-33(0) C) has proven to have the same neuroprotective properties without the detrimental effects of deep hypothermia. Mechanisms of injury that are exaggerated by moderate hyperthermia and ameliorated by hypothermia include, reduction of oxygen radical production, with peroxidase damage to lipids, proteins and DNA, microglial activation and ischemic depolarization, decrease in cerebral metabolic demand for oxygen and reduction of glycerin and excitatory amino acid (EAA) release. Studies have demonstrated that inflammation potentiates cerebral ischemic injury and that hypothermia can reduce neutrophil infiltration in ischemic regions. To further elucidate the mechanisms by which mild hypothermia produces neuroprotection in ischemia by attenuating the inflammatory response, we provoked inflammatory reaction, in brains of rats, dropping a substance that provokes a heavy inflammatory reaction. Two groups of ten animals underwent the same surgical procedure: the skull bone was partially removed, the duramater was opened and an inflammatory substance (5% carrageenin) was topically dropped. The scalp was sutured and, for the group that underwent neuroprotection, an ice bag was placed covering the entire skull surface, in order to maintain the brain temperature between 29,5-31(0) C during 120 minutes. After three days the animals were sacrificed and their brains were examined. The group protected by hypothermia demonstrated a remarkable reduction of polymorphonuclear leukocytes (PMNL) infiltration, indicating that mild hypothermia can have neuroprotective effects by reducing the inflammatory reaction.
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Northington, Frances J., Raul Chavez-Valdez, Ernest M. Graham, Sheila Razdan, Estelle B. Gauda i Lee J. Martin. "Necrostatin Decreases Oxidative Damage, Inflammation, and Injury after Neonatal HI". Journal of Cerebral Blood Flow & Metabolism 31, nr 1 (23.06.2010): 178–89. http://dx.doi.org/10.1038/jcbfm.2010.72.
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Necrostatin-1 inhibits receptor-interacting protein (RIP)-1 kinase and programmed necrosis and is neuroprotective in adult rodent models. Owing to the prominence of necrosis and continuum cell death in neonatal hypoxia–ischemia (HI), we tested whether necrostatin was neuroprotective in the developing brain. Postnatal day (P)7 mice were exposed to HI and injected intracerebroventricularly with 0.1 μL of 80 μmol necrostatin, Nec-1, 5-(1H-Indol-3-ylmethyl)-(2-thio-3-methyl) hydantoin, or vehicle. Necrostatin significantly decreased injury in the forebrain and thalamus at P11 and P28. There was specific neuroprotection in necrostatin-treated males. Necrostatin treatment decreased necrotic cell death and increased apoptotic cell death. Hypoxia–ischemia enforced RIP1–RIP3 complex formation and inhibited RIP3–FADD (Fas-associated protein with death domain) interaction, and these effects were blocked by necrostatin. Necrostatin also decreased HI-induced oxidative damage to proteins and attenuated markers of inflammation coincidental with decreased nuclear factor-κB and caspase 1 activation, and FLIP ((Fas-associated death-domain-like IL-1β-converting enzyme)-inhibitory protein) gene and protein expression. In this model of severe neonatal brain injury, we find that cellular necrosis can be managed therapeutically by a single dose of necrostatin, administered after HI, possibly by interrupting RIP1–RIP3-driven oxidative injury and inflammation. The effects of necrostatin treatment after HI reflect the importance of necrosis in the delayed phases of neonatal brain injury and represent a new direction for therapy of neonatal HI.
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Jiang, Bojing, Xiaotian Liu, Chao Yang, Zhongguang Yang, Jiren Luo, Songzi Kou, Kai Liu i Fei Sun. "Injectable, photoresponsive hydrogels for delivering neuroprotective proteins enabled by metal-directed protein assembly". Science Advances 6, nr 41 (październik 2020): eabc4824. http://dx.doi.org/10.1126/sciadv.abc4824.
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Axon regeneration constitutes a fundamental challenge for regenerative neurobiology, which necessitates the use of tailor-made biomaterials for controllable delivery of cells and biomolecules. An increasingly popular approach for creating these materials is to directly assemble engineered proteins into high-order structures, a process that often relies on sophisticated protein chemistry. Here, we present a simple approach for creating injectable, photoresponsive hydrogels via metal-directed assembly of His6-tagged proteins. The B12-dependent photoreceptor protein CarHC can complex with transition metal ions through an amino-terminal His6-tag, which can further undergo a sol-gel transition upon addition of AdoB12, leading to the formation of hydrogels with marked injectability and photodegradability. The inducible phase transitions further enabled facile encapsulation and release of cells and proteins. Injecting the Zn2+-coordinated gels decorated with leukemia inhibitory factor into injured mouse optic nerves led to prolonged cellular signaling and enhanced axon regeneration. This study illustrates a powerful strategy for designing injectable biomaterials.
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Barbalace, Maria Cristina, Lorenzo Zallocco, Daniela Beghelli, Maurizio Ronci, Serena Scortichini, Maria Digiacomo, Marco Macchia i in. "Antioxidant and Neuroprotective Activity of Extra Virgin Olive Oil Extracts Obtained from Quercetano Cultivar Trees Grown in Different Areas of the Tuscany Region (Italy)". Antioxidants 10, nr 3 (10.03.2021): 421. http://dx.doi.org/10.3390/antiox10030421.
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Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. In particular, extra-virgin olive oil (EVOO) phenols have been associated to neuroprotection. In this study, we investigated the potential antioxidant and neuroprotective activity of two different EVOO extracts obtained from Quercetano cultivar trees grown in two different areas (plain and hill) of the Tuscany region (Italy). The different geographical origin of the orchards influenced phenol composition. Plain extract presented a higher content of phenyl ethyl alcohols, cinnammic acids, oleacein, oleocanthal and flavones; meanwhile, hill extract was richer in lignans. Hill extract was more effective in protecting differentiated SH-SY5Y cells from peroxide stress thanks to a marked upregulation of the antioxidant enzymes heme oxygenase 1, NADPH quinone oxidoreductase 1, thioredoxin Reductase 1 and glutathione reductase. Proteomic analysis revealed that hill extract plays a role in the regulation of proteins involved in neuronal plasticity and activation of neurotrophic factors such as BDNF. In conclusion, these data demonstrate that EVOOs can have important neuroprotective activities, but these effects are strictly related to their specific phenol composition.
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Bordet, Régis, Dominique Deplanque, Patrice Maboudou, François Puisieux, Qian Pu, Emmanuel Robin, Annie Martin i in. "Increase in Endogenous Brain Superoxide Dismutase as a Potential Mechanism of Lipopolysaccharide-Induced Brain Ischemic Tolerance". Journal of Cerebral Blood Flow & Metabolism 20, nr 8 (sierpień 2000): 1190–96. http://dx.doi.org/10.1097/00004647-200008000-00004.
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A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before 60-minute middle cerebral artery occlusion, induced a delayed neuroprotection proven by the significant decrease (–35%) of brain infarct volume in comparison with control, whereas infarct volumes remained unchanged in rats treated 12, 24, or 168 hours before ischemia. This delayed neuroprotective effect of LPS was induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in the cortical part of the infarcted zone, not in the subcortical part. The beneficial effect of LPS on consequences of middle cerebral artery occlusion was suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/kg) administered 1 hour before LPS, whereas both drugs had no direct effect on infarct volume by themselves, suggesting that activation of inflammatory pathway is involved in the development of LPS-induced brain ischemic tolerance. Preadministration of cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain ischemic tolerance suggesting that a protein synthesis is also necessary as a mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized proteins because lipopolysaccharide increased SOD brain activity 72 hours, but not 12 hours, after its administration, which paralleled the development of brain ischemic tolerance. In contrast, catalase brain activity remained unchanged after LPS administration. The LPS-induced delayed increase in SOD brain content was suppressed by a previous administration of indomethacin. These data suggest that the delayed neuroprotective effect of low doses of LPS is mediated by an increased synthesis of brain SOD that could be triggered by activation of inflammatory pathway.
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Li, Fengwu, Xiaokun Geng, James Yip i Yuchuan Ding. "Therapeutic Target and Cell-signal Communication of Chlorpromazine and Promethazine in Attenuating Blood–Brain Barrier Disruption after Ischemic Stroke". Cell Transplantation 28, nr 2 (20.12.2018): 145–56. http://dx.doi.org/10.1177/0963689718819443.
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Ischemic stroke destroys blood–brain barrier (BBB) integrity. There are currently no effective treatments available in the clinical setting. Post-ischemia treatment with phenothiazine drugs [combined chlorpromazine and promethazine (C+P)] has been shown to be neuroprotective in stroke. The present study determined the effect of C+P in BBB integrity. Sprague-Dawley rats were divided into the following groups ( n=8 each): (1) stroke, (2) stroke treated by C+P with temperature control, and (3) stroke treated by C+P without temperature control. Infarct volume and neurological deficits were measured to assess the neuroprotective effect of C+P. BBB permeability was determined by brain edema and Evans blue leakage. Expression of BBB integral molecules, including proteins of aquaporin-4 and -9 (AQP-4, AQP-9), matrix metalloproteinase-2 and -9 (MMP-2, MMP-9), zonula occludens-1 (ZO-1), claudin-1/5, occludin, and laminin were determined by Western blot. Stroke caused brain infarction and neurological deficits, as well as BBB damage, which were all attenuated by C+P through drug-induced hypothermia. When the reduced temperature was controlled to physiological levels, C+P still conferred neuroprotection, suggesting a therapeutic effect independent of hypothermia. Furthermore, C+P significantly attenuated the increase in AQP-4, AQP-9, MMP-2, and MMP-9 levels after stroke, and reversed the decrease in tight junction protein (ZO-1, claudin-1/5, occludin) and basal laminar protein (laminin) levels. This study clearly indicates a beneficial effect of C+P on BBB integrity after stroke, which may be independent of drug-induced hypothermia. These findings further prove the clinical target and cell-signal communication of C+P treatment, which may direct us closer toward the development of an efficacious neuroprotective therapy.
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Cuanalo-Contreras, Karina, i Ines Moreno-Gonzalez. "Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases". International Journal of Molecular Sciences 20, nr 19 (20.09.2019): 4666. http://dx.doi.org/10.3390/ijms20194666.
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Proteins play crucial and diverse roles within the cell. To exert their biological function they must fold to acquire an appropriate three-dimensional conformation. Once their function is fulfilled, they need to be properly degraded to hamper any possible damage. Protein homeostasis or proteostasis comprises a complex interconnected network that regulates different steps of the protein quality control, from synthesis and folding, to degradation. Due to the primary role of proteins in cellular function, the integrity of this network is critical to assure functionality and health across lifespan. Proteostasis failure has been reported in the context of aging and neurodegeneration, such as Alzheimer’s and Parkinson’s disease. Therefore, targeting the proteostasis elements emerges as a promising neuroprotective therapeutic approach to prevent or ameliorate the progression of these disorders. A variety of natural products are known to be neuroprotective by protein homeostasis interaction. In this review, we will focus on the current knowledge regarding the use of natural products as modulators of different components of the proteostasis machinery within the framework of age-associated neurodegenerative diseases.
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Mattson, Mark P., Sic L. Chan i Wenzhen Duan. "Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior". Physiological Reviews 82, nr 3 (7.01.2002): 637–72. http://dx.doi.org/10.1152/physrev.00004.2002.
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Multiple molecular, cellular, structural, and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively, or they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. Multiple mechanisms are employed to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands and promote recovery of function after injury. The mechanisms include production of neurotrophic factors and cytokines, expression of various cell survival-promoting proteins (e.g., protein chaperones, antioxidant enzymes, Bcl-2 and inhibitor of apoptosis proteins), preservation of genomic integrity by telomerase and DNA repair proteins, and mobilization of neural stem cells to replace damaged neurons and glia. The aging process challenges such neuroprotective and neurorestorative mechanisms. Genetic and environmental factors superimposed upon the aging process can determine whether brain aging is successful or unsuccessful. Mutations in genes that cause inherited forms of Alzheimer's disease (amyloid precursor protein and presenilins), Parkinson's disease (α-synuclein and Parkin), and trinucleotide repeat disorders (huntingtin, androgen receptor, ataxin, and others) overwhelm endogenous neuroprotective mechanisms; other genes, such as those encoding apolipoprotein E4, have more subtle effects on brain aging. On the other hand, neuroprotective mechanisms can be bolstered by dietary (caloric restriction and folate and antioxidant supplementation) and behavioral (intellectual and physical activities) modifications. At the cellular and molecular levels, successful brain aging can be facilitated by activating a hormesis response in which neurons increase production of neurotrophic factors and stress proteins. Neural stem cells that reside in the adult brain are also responsive to environmental demands and appear capable of replacing lost or dysfunctional neurons and glial cells, perhaps even in the aging brain. The recent application of modern methods of molecular and cellular biology to the problem of brain aging is revealing a remarkable capacity within brain cells for adaptation to aging and resistance to disease.
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Chen, Wen-Ying, Cheng-Yi Chang, Jian-Ri Li, Jiaan-Der Wang, Chih-Cheng Wu, Yu-Hsiang Kuan, Su-Lan Liao, Wen-Yi Wang i Chun-Jung Chen. "Anti-inflammatory and Neuroprotective Effects of Fungal Immunomodulatory Protein Involving Microglial Inhibition". International Journal of Molecular Sciences 19, nr 11 (21.11.2018): 3678. http://dx.doi.org/10.3390/ijms19113678.
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Microglia polarization of classical activation state is crucial to the induction of neuroinflammation, and has been implicated in the pathogenesis of numerous neurodegenerative diseases. Fungal immunomodulatory proteins are emerging health-promoting natural substances with multiple pharmacological activities, including immunomodulation. Herein, we investigated the anti-inflammatory and neuroprotective potential of fungal immunomodulatory protein extracted from Ganoderma microsporum (GMI) in an in vitro rodent model of primary cultures. Using primary neuron/glia cultures consisting of neurons, astrocytes, and microglia, a GMI showed an alleviating effect on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced inflammatory mediator production and neuronal cell death. The events of neuroprotection caused by GMI were accompanied by the suppression of Nitric Oxide (NO), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), and Prostaglandin E2 (PGE2) production, along with the inhibition of microglia activation. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by GMI was accompanied by the resolution of oxidative stress, the preservation of protein tyrosine phosphatase and serine/threonine phosphatase activity, and the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein (CREB), along with signal transducers and activators of transcription (Stat1) transcriptional activities and associated upstream activators. These findings suggest that GMI may have considerable potential towards the treatment of neuroinflammation-mediated neurodegenerative diseases.
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Tripathy, Debjani, Alma Sanchez, Xiangling Yin, Joseph Martinez i Paula Grammas. "Age-related decrease in cerebrovascular-derived neuroprotective proteins: Effect of acetaminophen". Microvascular Research 84, nr 3 (listopad 2012): 278–85. http://dx.doi.org/10.1016/j.mvr.2012.08.004.
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Kamisuki, Shinji, Natsumi Himeno, Yukine Tsurukawa, Tomoe Kusayanagi, Masahiro Takeno, Takashi Kamakura, Kouji Kuramochi i Fumio Sugawara. "Identification of proteins that bind to the neuroprotective agent neoechinulin A". Bioscience, Biotechnology, and Biochemistry 82, nr 3 (15.02.2018): 442–48. http://dx.doi.org/10.1080/09168451.2018.1433018.
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Reukov, Vladimir, Victor Maximov i Alexey Vertegel. "Proteins conjugated to poly(butyl cyanoacrylate) nanoparticles as potential neuroprotective agents". Biotechnology and Bioengineering 108, nr 2 (26.10.2010): 243–52. http://dx.doi.org/10.1002/bit.22958.
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Benarroch, E. E. "Heat shock proteins: Multiple neuroprotective functions and implications for neurologic disease". Neurology 76, nr 7 (14.02.2011): 660–67. http://dx.doi.org/10.1212/wnl.0b013e31820c3119.
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Medvedev, Alexei, Arthur Kopylov, Olga Buneeva, Leonid Kurbatov, Olga Tikhonova, Alexis Ivanov i Victor Zgoda. "A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research". International Journal of Molecular Sciences 21, nr 11 (11.06.2020): 4187. http://dx.doi.org/10.3390/ijms21114187.
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Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes.
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Pomin, Vitor H., Fakhri Mahdi, Weihua Jin, Fuming Zhang, Robert J. Linhardt i Jason J. Paris. "Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat". Pharmaceuticals 14, nr 8 (23.07.2021): 714. http://dx.doi.org/10.3390/ph14080714.
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The potential neuroprotective capacity of four different sulfated glycans: Botryocladia occidentalis-derived sulfated galactan (BoSG) (MW > 100 kDa), Lytechinus variegatus-derived sulfated fucan (LvSF) (MW~90 kDa), high-molecular weight dextran sulfate (DxS) (MW 100 kDa), and unfractionated heparin (UFH) (MW~15 kDa), was assessed in response to the HIV-1 proteins, R5-tropic glycoprotein 120 (gp120) and/or trans-activator of transcription (Tat), using primary murine neurons co-cultured with mixed glia. Compared to control-treated cells in which HIV-1 proteins alone or combined were neurotoxic, BoSG was, among the four tested sulfated glycans, the only one capable of showing significant concentration-dependent neuroprotection against Tat and/or gp120, alone or combined. Surface plasmon resonance-based data indicate that BoSG can bind both HIV-1 proteins at nM concentrations with preference for Tat (7.5 × 10−8 M) over gp120 (3.2 × 10−7 M) as compared to UFH, which bound gp120 (8.7 × 10−7 M) over Tat (5.7 × 10−6 M). Overall, these data support the notion that sulfated glycan extracted from the red alga B. occidentalis, BoSG, can exert neuroprotection against HIV-1 Tat and gp120, potentially via direct molecular interactions.
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Moreno, Beatriz, i Pablo Villoslada. "Neuroprotective Therapies for Multiple Sclerosis". European Neurological Review 7, nr 3 (2012): 189. http://dx.doi.org/10.17925/enr.2012.07.03.189.
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Multiple sclerosis (MS) is considered to be an autoimmune disease that is caused by the immune system attacking the central nervous system (CNS) leading to myelin loss and axonal damage, resulting in long-term disability. The pathophysiology of MS is complex with involvement of genetic and environmental factors that define the susceptibility to generate the autoimmune attack. In the last decade, several immunomodulatory drugs have been approved, including recombinant proteins such as interferon-beta, monoclonal antibodies such as natalizumab, or small chemicals including glatiramer acetate. In addition, there is a wide pipeline of new immunomodulators finishing Phase II or III trials. However, at present there are no approved treatments that directly reduce nervous system damage or enhance its repair. Novel neuroprotective agents have been identified in pre-clinical studies but their development is being prevented by the absence of appropriate understanding of the mechanisms of CNS damage by inflammation as well as by the lack of clinical platforms to test them. In this review, we describe the different mechanisms of axonal injury and discuss some of the principal therapeutic candidates that could provide neuroprotection in MS.
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Relat, Julia, Julio Come, Belen Perez, Pelayo Camps, Diego Muñoz-Torrero, Albert Badia, Lydia Gimenez-Llort i M. Clos. "Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice". International Journal of Molecular Sciences 19, nr 9 (4.09.2018): 2615. http://dx.doi.org/10.3390/ijms19092615.
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Molecular factors involved in neuroprotection are key in the design of novel multitarget drugs in aging and neurodegeneration. AVCRI104P3 is a huprine derivative that exhibits potent inhibitory effects on human AChE, BuChE, and BACE-1 activities, as well as on AChE-induced and self-induced Aβ aggregation. More recently, cognitive protection and anxiolytic-like effects have also been reported in mice treated with this compound. Now, we have assessed the ability of AVCRI104P3 (0.43 mg/kg, 21 days) to modulate the levels of some proteins involved in the anti-apoptotic/apoptotic processes (pAkt1, Bcl2, pGSK3β, p25/p35), inflammation (GFAP and Iba1) and neurogenesis in C57BL/6 mice. The effects of AVCRI104P3 on AChE-R/AChE-S isoforms have been also determined. We have observed that chronic treatment of C57BL/6 male mice with AVCRI104P3 results in neuroprotective effects, increasing significantly the levels of pAkt1 and pGSK3β in the hippocampus and Bcl2 in both hippocampus and cortex, but slightly decreasing synaptophysin levels. Astrogliosis and neurogenic markers GFAP and DCX remained unchanged after AVCRI104P3 treatment, whereas microgliosis was found to be significantly decreased pointing out the involvement of this compound in inflammatory processes. These results suggest that the neuroprotective mechanisms that are behind the cognitive and anxiolytic effects of AVCRI104P3 could be partly related to the potentiation of some anti-apoptotic and anti-inflammatory proteins and support the potential of AVCRI104P3 for the treatment of brain dysfunction associated with aging and/or dementia.
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Wu, Ying, Zheng-cai Li, Li-qing Yao, Mai Li i Mei Tang. "Schisandrin B alleviates acute oxidative stress via modulation of the Nrf2/Keap1-mediated antioxidant pathway". Applied Physiology, Nutrition, and Metabolism 44, nr 1 (styczeń 2019): 1–6. http://dx.doi.org/10.1139/apnm-2018-0251.
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Schisandrin B (Sch B), one of the main effective components of the dried fruit of Schisandra chinensis, protects neurons from oxidative stress in the central nervous system. Here we investigated the neuroprotective effect of Sch B against damage caused by acute oxidative stress and attempted to define the possible mechanisms. Using the elevated plus maze and open field test, we found that forced swimming, an acute stressor, significantly induced anxiety-like behavior that was alleviated by oral Sch B treatment. In addition, the Sch B treatment reduced toxicity, malondialdehyde levels, and production of reactive oxygen species, an important factor for neuron damage. Antioxidants under the control of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, such as superoxide dismutase and glutathione, were significantly increased by Sch B treatment. Moreover, a higher percentage of intact cells in the amygdala of treated mice, revealed by Nissl staining, further verified the neuroprotective effect of Sch B. Several proteins, such as Nrf2 and its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1), were abnormally expressed in mice subjected to forced swimming, but this abnormal expression was significantly reversed by Sch B treatment. Our results suggest that Sch B may be a potential therapeutic agent against anxiety associated with oxidative stress. The possible mechanism is neuroprotection through enhanced antioxidant activity.
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Bonafede, Brandi, Manfredi, Scambi, Schiaffino, Merigo, Turano i in. "The Anti-Apoptotic Effect of ASC-Exosomes in an In Vitro ALS Model and Their Proteomic Analysis". Cells 8, nr 9 (14.09.2019): 1087. http://dx.doi.org/10.3390/cells8091087.
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Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 α, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases.