Journal articles on the topic 'Cerebral neurodegenerative disease'
To see the other types of publications on this topic, follow the link: Cerebral neurodegenerative disease.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Cerebral neurodegenerative disease.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Bass, Nancy. "Cerebral palsy and neurodegenerative disease." Current Opinion in Pediatrics 11, no. 6 (December 1999): 504–7. http://dx.doi.org/10.1097/00008480-199912000-00005.
Full text
2
Maruyama, Hirofumi. "Cerebral blood flow of neurodegenerative disease." Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism) 28, no. 2 (2017): 337–39. http://dx.doi.org/10.16977/cbfm.28.2_337.
Full text
3
Dusek, Petr, Tim Hofer, Jan Alexander, Per M. Roos, and Jan O. Aaseth. "Cerebral Iron Deposition in Neurodegeneration." Biomolecules 12, no. 5 (May 17, 2022): 714. http://dx.doi.org/10.3390/biom12050714.
Full textAbstract:
Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson’s disease, Friedreich’s disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood–brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.
4
Trujillo-Estrada, Laura, Angela Gomez-Arboledas, Stefânia Forner, Alessandra Cadete Martini, Antonia Gutierrez, David Baglietto-Vargas, and Frank M. LaFerla. "Astrocytes: From the Physiology to the Disease." Current Alzheimer Research 16, no. 8 (October 11, 2019): 675–98. http://dx.doi.org/10.2174/1567205016666190830110152.
Full textAbstract:
Astrocytes are key cells for adequate brain formation and regulation of cerebral blood flow as well as for the maintenance of neuronal metabolism, neurotransmitter synthesis and exocytosis, and synaptic transmission. Many of these functions are intrinsically related to neurodegeneration, allowing refocusing on the role of astrocytes in physiological and neurodegenerative states. Indeed, emerging evidence in the field indicates that abnormalities in the astrocytic function are involved in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In the present review, we highlight the physiological role of astrocytes in the CNS, including their communication with other cells in the brain. Furthermore, we discuss exciting findings and novel experimental approaches that elucidate the role of astrocytes in multiple neurological disorders.
5
Turturici, Giuseppina, Gabriella Sconzo, and Fabiana Geraci. "Hsp70 and Its Molecular Role in Nervous System Diseases." Biochemistry Research International 2011 (2011): 1–18. http://dx.doi.org/10.1155/2011/618127.
Full textAbstract:
Heat shock proteins (HSPs) are induced in response to many injuries including stroke, neurodegenerative disease, epilepsy, and trauma. The overexpression of one HSP in particular, Hsp70, serves a protective role in several different models of nervous system injury, but has also been linked to a deleterious role in some diseases. Hsp70 functions as a chaperone and protects neurons from protein aggregation and toxicity (Parkinson disease, Alzheimer disease, polyglutamine diseases, and amyotrophic lateral sclerosis), protects cells from apoptosis (Parkinson disease), is a stress marker (temporal lobe epilepsy), protects cells from inflammation (cerebral ischemic injury), has an adjuvant role in antigen presentation and is involved in the immune response in autoimmune disease (multiple sclerosis). The worldwide incidence of neurodegenerative diseases is high. As neurodegenerative diseases disproportionately affect older individuals, disease-related morbidity has increased along with the general increase in longevity. An understanding of the underlying mechanisms that lead to neurodegeneration is key to identifying methods of prevention and treatment. Investigators have observed protective effects of HSPs induced by preconditioning, overexpression, or drugs in a variety of models of brain disease. Experimental data suggest that manipulation of the cellular stress response may offer strategies to protect the brain during progression of neurodegenerative disease.
6
Salvadori, Claudia, Laura Lossi, Mario Arispici, and Carlo Cantile. "Spongiform neurodegenerative disease in a Persian kitten." Journal of Feline Medicine and Surgery 9, no. 3 (June 2007): 242–45. http://dx.doi.org/10.1016/j.jfms.2006.12.001.
Full textAbstract:
A congenital encephalopathy with spongiform degeneration and prominent neuronal apoptosis was observed in a 4-month-old Persian male cat with a history of depressed mental status and ataxia. On clinical examination, signs included right head tilt, ventroflexion of the head and neck, and tetraparesis. Histological examination of the central nervous system revealed multifocal, bilateral and symmetrical vacuolar degeneration of the neuropil, mainly involving the cerebellar and vestibular nuclei area, the caudal colliculi, the mesencephalic nuclei, the tegmental area and the deeper layer of the cerebral cortex. Accumulation of phosphorylated neurofilaments was detected in neuronal perikarya of the deep cortical layers, hippocampus and thalamus. Numerous pyknotic and apoptotic neurons were also observed in the cerebral cortex. These neuropathological changes differ from those observed in previous reports of spongiform degeneration of the grey matter in cats and were suggestive of a congenital neurodegenerative disease.
7
Beaman, Charles, Krystyna Kozii, Saima Hilal, Minghua Liu, Anthony J. Spagnolo-Allende, Guillermo Polanco-Serra, Christopher Chen, et al. "Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration." Neurology 98, no. 16 (February 28, 2022): e1605-e1616. http://dx.doi.org/10.1212/wnl.0000000000200142.
Full textAbstract:
Background and ObjectivesAge-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer disease. However, in the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA affect volumetric changes in the brain related to neurodegenerative disease remains unclear.MethodsWe performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between 2 related markers of cerebrovascular disease—MRI-based CMBs and autopsy-based CAA—as independent variables and volumetric markers of neurodegeneration as dependent variables. NOMAS included mostly dementia-free participants age 55 years or older from northern Manhattan. ADNI included participants living in the United States age 55–90 years with a range of cognitive status. EDIS included community-based participants living in Singapore age 60 years and older with a range of cognitive status. BARS included postmortem pathologic samples.ResultsWe included 2,657 participants with available MRI data and 82 autopsy cases from BARS. In a meta-analysis of NOMAS, ADNI, and EDIS, superficial CMBs were associated with larger gray matter (β = 4.49 ± 1.13, p = 0.04) and white matter (β = 4.72 ± 2.1, p = 0.03) volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with 1 CMB (β = 5.17 ± 2.47, p = 0.04) than in those with ≥2 CMBs (β = 1.97 ± 3.41, p = 0.56). In BARS, CAA was associated with increased cortical thickness (β = 6.5 ± 2.3, p = 0.016) but not with increased brain weight (β = 1.54 ± 1.29, p = 0.26).DiscussionSuperficial CMBs are associated with larger morphometric brain measures, specifically white matter volume. This association is strongest in brains with fewer CMBs, suggesting that the CMB/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease.
8
Yadav, Dharmendra Kumar. "Potential Therapeutic Strategies of Phytochemicals in Neurodegenerative Disorders." Current Topics in Medicinal Chemistry 21, no. 31 (December 23, 2021): 2814–38. http://dx.doi.org/10.2174/1568026621666211201150217.
Full textAbstract:
Neurodegeneration is a syndrome that occurs through the loss of the neuronal system's structure and function. In the 21st century, major health issues are related to cognitive impairment and neurological disorders such as autism, learning disabilities, Huntington’s, cerebral palsy, schizophrenia, Alzheimer's, neuromuscular, lateral sclerosis, and Parkinson’s disease may be life-threatening. Various experimental and epidemiological studies reveal the risk factors associated with the disease, like oxidative stress, hypertension, antioxidant enzyme abnormalities, metabolic toxicity, advanced age, cytoskeletal abnormalities, genetic defects, autoimmunity, mineral deficiencies, and other vascular disorders. Various compounds have been screened for the treatment of neurodegenerative diseases (NDs), but, due to their side effects, they have solitary symptomatic benefits. Phytochemicals play a crucial role in maintaining the chemical balance of the brain by affecting the receptor function of specific inhibitory neurotransmitters. This review highlights the importance of phytochemicals for neurodegenerative diseases, in particular the possible mechanism of action of these natural compounds used for the treatment.
9
Ribe, Elena M., Esther Serrano-Saiz, Nsikan Akpan, and Carol M. Troy. "Mechanisms of neuronal death in disease: defining the models and the players." Biochemical Journal 415, no. 2 (September 25, 2008): 165–82. http://dx.doi.org/10.1042/bj20081118.
Full textAbstract:
Dysregulation of life and death at the cellular level leads to a variety of diseases. In the nervous system, aberrant neuronal death is an outstanding feature of neurodegenerative diseases. Since the discovery of the caspase family of proteases, much effort has been made to determine how caspases function in disease, including neurodegenerative diseases. Although many papers have been published examining caspases in neuronal death and disease, the pathways have not been fully clarified. In the present review, we examine the potential players in the death pathways, the current tools for examining these players and the models for studying neurological disease. Alzheimer's disease, the most common neurodegenerative disorder, and cerebral ischaemia, the most common cause of neurological death, are used to illustrate our current understanding of death signalling in neurodegenerative diseases. A better understanding of the neuronal death pathways would provide targets for the development of therapeutic interventions for these diseases.
10
Accogli, Andrea, Kether Guerrero, Maria Daniela D’Agostino, Luan Tran, Cécile Cieuta-Walti, Isabelle Thiffault, Sébastien Chénier, Jeremy Schwartzentruber, Jacek Majewski, and Geneviève Bernard. "Biallelic Loss-of-Function Variants in AIMP1 Cause a Rare Neurodegenerative Disease." Journal of Child Neurology 34, no. 2 (November 28, 2018): 74–80. http://dx.doi.org/10.1177/0883073818811223.
Full textAbstract:
AIMP1/p43, is a noncatalytic component of the mammalian multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their cognate tRNAs. AIMP1 is largely expressed in the central nervous system, where it is part of the regulatory machine of the neurofilament assembly, playing a crucial role in neuronal development and function. To date, nonsense mutations in AIMP1 have been associated with a primary neurodegenerative disorder consisting of cerebral atrophy, hypomyelination, microcephaly and epilepsy, whereas missense mutations have recently been linked to intellectual disability without neurodegeneration. Here, we report the first French-Canadian patient with a novel frameshift AIMP1 homozygous mutation (c.191_192delAA, p.Gln64Argfs*25), resulting in a severe neurodegenerative phenotype. We review and discuss the phenotypic spectrum associated with AIMP1 pathogenic variants.
11
Gandhi, Rozil, Ritu Kakkar, Sajeev Rajan, Rashmi Bhangale, and Shrinivas Desai. "Menkes Kinky Hair Syndrome: A Rare Neurodegenerative Disease." Case Reports in Radiology 2012 (2012): 1–4. http://dx.doi.org/10.1155/2012/684309.
Full textAbstract:
Menkes kinky hair disease is a rare X-linked recessive disease nearly exclusively affecting males who present at 2-3 months of age due to abnormal functioning of copper-dependent enzymes due to deficiency of copper. Here, we describe a completely worked-up case of a 4-month-old male infant with very typical history and radiological features confirmed by biochemical and trichoanalysis. The initially seen asymmetric cortical and subcortical T2 hyperintensities in cerebral and cerebellar hemispheres converted into symmetrical diffuse cerebral and predominantly cerebellar atrophy with uniform loss of both white and grey matter on follow-up MRI. Also, subdural hemorrhages of various sizes and different stages and tortuosity of larger proximal intracranial vessels with distal narrowing were identified. Ours is a completely worked-up proven case of Menkes kinky hair disease (MKHD) with history, electroencephalography, biochemical, trichoanalysis, and MRI findings. This is a good teaching case and shows importance of clinical examination and biochemistry as complimentary to MRI. Tortuous intracranial arteries with blocked major vessels are found only in this disease, thus stressing the value of MR Angiography in these patients.
12
Boyarchuk, O. R. "Interstitial lung disease and neurodegeneration in FINCA syndrome: new knowledge changes old judgments." Modern pediatrics. Ukraine, no. 5(125) (September 30, 2022): 103–7. http://dx.doi.org/10.15574/sp.2022.125.103.
Full textAbstract:
FINCA (Fibrosis, Neurodegeneration, Cerebral Angiomatosis) syndrome is a new genetic multiorgan disease caused by a mutation in NHLRC2 (NHL repeat-containing protein 2). Disease manifests at an early age by interstitial lung disease, neurodegenerative disorders, hemolytic anemia, gastrointestinal disorders, liver dysfunction and other multiorgan changes. The syndrome was first described in 2018 in three children who died before the age of two. Studies in recent years have significantly expanded the range of clinical symptoms of FINCA syndrome, and also showed great variability in the severity of the symptomes, especially respiratory lesions. Taking into account the neurological problems in all described patients, NHLRC2 should be included in the sequencing panels of neurological diseases (neurodegenerative, neurodevelopmental disorders, epilepsy). Recurrent respiratory infections and episodic diarrhea, as well as hypogammaglobulinemia in most patients require study of the role of NHLRC2 protein in the functioning of the immune system. No conflict of interests was declared by the authors.
13
Clark, I. A., and B. Vissel. "Broader Insights into Understanding Tumor Necrosis Factor and Neurodegenerative Disease Pathogenesis Infer New Therapeutic Approaches." Journal of Alzheimer's Disease 79, no. 3 (February 2, 2021): 931–48. http://dx.doi.org/10.3233/jad-201186.
Full textAbstract:
Proinflammatory cytokines such as tumor necrosis factor (TNF), with its now appreciated key roles in neurophysiology as well as neuropathophysiology, are sufficiently well-documented to be useful tools for enquiry into the natural history of neurodegenerative diseases. We review the broader literature on TNF to rationalize why abruptly-acquired neurodegenerative states do not exhibit the remorseless clinical progression seen in those states with gradual onsets. We propose that the three typically non-worsening neurodegenerative syndromes, post-stroke, post-traumatic brain injury (TBI), and post cardiac arrest, usually become and remain static because of excess cerebral TNF induced by the initial dramatic peak keeping microglia chronically activated through an autocrine loop of microglial activation through excess cerebral TNF. The existence of this autocrine loop rationalizes post-damage repair with perispinal etanercept and proposes a treatment for cerebral aspects of COVID-19 chronicity. Another insufficiently considered aspect of cerebral proinflammatory cytokines is the fitness of the endogenous cerebral anti-TNF system provided by norepinephrine (NE), generated and distributed throughout the brain from the locus coeruleus (LC). We propose that an intact LC, and therefore an intact NE-mediated endogenous anti-cerebral TNF system, plus the DAMP (damage or danger-associated molecular pattern) input having diminished, is what allows post-stroke, post-TBI, and post cardiac arrest patients a strong long-term survival advantage over Alzheimer’s disease and Parkinson’s disease sufferers. In contrast, Alzheimer’s disease and Parkinson’s disease patients remorselessly worsen, being handicapped by sustained, accumulating, DAMP and PAMP (pathogen-associated molecular patterns) input, as well as loss of the LC-origin, NE-mediated, endogenous anti-cerebral TNF system. Adrenergic receptor agonists may counter this.
14
Park, Han-A., Mary Margaret Hayden, Sydni Bannerman, Joseph Jansen, and Kristi M. Crowe-White. "Anti-Apoptotic Effects of Carotenoids in Neurodegeneration." Molecules 25, no. 15 (July 29, 2020): 3453. http://dx.doi.org/10.3390/molecules25153453.
Full textAbstract:
Apoptosis, programmed cell death type I, is a critical part of neurodegeneration in cerebral ischemia, Parkinson’s, and Alzheimer’s disease. Apoptosis begins with activation of pro-death proteins Bax and Bak, release of cytochrome c and activation of caspases, loss of membrane integrity of intracellular organelles, and ultimately cell death. Approaches that block apoptotic pathways may prevent or delay neurodegenerative processes. Carotenoids are a group of pigments found in fruits, vegetables, and seaweeds that possess antioxidant properties. Over the last several decades, an increasing number of studies have demonstrated a protective role of carotenoids in neurodegenerative disease. In this review, we describe functions of commonly consumed carotenoids including lycopene, β-carotene, lutein, astaxanthin, and fucoxanthin and their roles in neurodegenerative disease models. We also discuss the underlying cellular mechanisms of carotenoid-mediated neuroprotection, including their antioxidant properties, role as signaling molecules, and as gene regulators that alleviate apoptosis-associated brain cell death.
15
Martin, Antonio, Giulia De Vivo, and Vittorio Gentile. "Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases." International Journal of Alzheimer's Disease 2011 (2011): 1–8. http://dx.doi.org/10.4061/2011/865432.
Full textAbstract:
Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Parkinson's disease, supranuclear palsy, Huntington's disease, and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This paper focuses on the possible molecular mechanisms by which transglutaminase activity could be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases, and on the possible therapeutic effects of selective transglutaminase inhibitors for the cure of patients with diseases characterized by aberrant transglutaminase activity.
16
Heron, Campbell J. Le, Sarah L. Wright, Tracy R. Melzer, Daniel J. Myall, Michael R. MacAskill, Leslie Livingston, Ross J. Keenan, Richard Watts, John C. Dalrymple-Alford, and Tim J. Anderson. "Comparing Cerebral Perfusion in Alzheimer's Disease and Parkinson's Disease Dementia: An ASL-MRI Study." Journal of Cerebral Blood Flow & Metabolism 34, no. 6 (March 12, 2014): 964–70. http://dx.doi.org/10.1038/jcbfm.2014.40.
Full textAbstract:
Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD < PDD) and right frontal cortex (PDD < AD). In conclusion, the pattern of cerebral hypoperfusion is very similar in AD and PDD. This suggests closely linked mechanisms of neurodegeneration mediating the evolution of dementia in both conditions.
17
Maciejczyk, Mateusz, Anna Zalewska, and Karolina Gerreth. "Salivary Redox Biomarkers in Selected Neurodegenerative Diseases." Journal of Clinical Medicine 9, no. 2 (February 12, 2020): 497. http://dx.doi.org/10.3390/jcm9020497.
Full textAbstract:
Neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are disorders, which cause irreversible and progressive deterioration of the central nervous system. The pathophysiology of NDDs is still not fully explained; nevertheless, oxidative stress is considered as a critical mediator of cerebral degeneration, brain inflammation, as well as neuronal apoptosis. Therefore, it is not surprising that redox biomarkers are increasingly used in the diagnosis of neurodegenerative diseases. As saliva is a very easy to obtain bioliquid, it seems promising to use this biomaterial in the diagnosis of NDDs. Saliva collection is easy, cheap, stress-free, and non-infectious, and it does not require the help of a specialised medical personnel. Additionally, the concentrations of many salivary redox biomarkers correlate with their content in blood serum as well as the degree of disease progression, which makes them non-invasive indicators of NDDs. This paper reviews the latest knowledge concerning the use of salivary redox biomarkers in the diagnosis and prognosis of selected neurodegenerative diseases.
18
Grossmann, Klaus. "Anticoagulants for Treatment of Alzheimer’s Disease." Journal of Alzheimer's Disease 77, no. 4 (October 13, 2020): 1373–82. http://dx.doi.org/10.3233/jad-200610.
Full textAbstract:
Alzheimer’s disease (AD) is a multifactorial syndrome with a plethora of progressive, degenerative changes in the brain parenchyma, but also in the cerebrovascular and hemostatic system. A therapeutic approach for AD is reviewed, which is focused on the role of amyloid–β protein (Aβ) and fibrin in triggering intra-brain vascular dysfunction and connected, cognitive decline. It is proposed that direct oral anticoagulants (DOACs) counteract Aβ-induced pathological alterations in cerebral blood vessels early in AD, a condition, known as cerebral amyloid angiopathy (CAA). By inhibiting thrombin for fibrin formation, anticoagulants can prevent accumulations of proinflammatory thrombin and fibrin, and deposition of degradation-resistant, Aβ-containing fibrin clots. These fibrin–Aβ clots are found in brain parenchyma between neuron cells, and in and around cerebral blood vessels in areas of CAA, leading to decreased cerebral blood flow. Consequently, anticoagulant treatment could reduce hypoperfusion and restricted supply of brain tissue with oxygen and nutrients. Concomitantly, hypoperfusion-enhanced neurodegenerative processes, such as progressive Aβ accumulation via synthesis and reduced perivascular clearance, neuroinflammation, and synapse and neuron cell loss, could be mitigated. Given full cerebral perfusion and reduced Aβ- and fibrin-accumulating and inflammatory milieu, anticoagulants could be able to decrease vascular-driven progression in neurodegenerative and cognitive changes, present in AD, when treated early, therapeutically, or prophylactically.
19
D’Mello, Santosh R. "When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer’s and Huntington’s Disease." International Journal of Molecular Sciences 22, no. 11 (May 31, 2021): 5911. http://dx.doi.org/10.3390/ijms22115911.
Full textAbstract:
Alzheimer’s disease (AD) is a mostly sporadic brain disorder characterized by cognitive decline resulting from selective neurodegeneration in the hippocampus and cerebral cortex whereas Huntington’s disease (HD) is a monogenic inherited disorder characterized by motor abnormalities and psychiatric disturbances resulting from selective neurodegeneration in the striatum. Although there have been numerous clinical trials for these diseases, they have been unsuccessful. Research conducted over the past three decades by a large number of laboratories has demonstrated that abnormal actions of common kinases play a key role in the pathogenesis of both AD and HD as well as several other neurodegenerative diseases. Prominent among these kinases are glycogen synthase kinase (GSK3), p38 mitogen-activated protein kinase (MAPK) and some of the cyclin-dependent kinases (CDKs). After a brief summary of the molecular and cell biology of AD and HD this review covers what is known about the role of these three groups of kinases in the brain and in the pathogenesis of the two neurodegenerative disorders. The potential of targeting GSK3, p38 MAPK and CDKS as effective therapeutics is also discussed as is a brief discussion on the utilization of recently developed drugs that simultaneously target two or all three of these groups of kinases. Multi-kinase inhibitors either by themselves or in combination with strategies currently being used such as immunotherapy or secretase inhibitors for AD and knockdown for HD could represent a more effective therapeutic approach for these fatal neurodegenerative diseases.
20
Ficiarà, Eleonora, Ilaria Stura, and Caterina Guiot. "Iron Transport across Brain Barriers: Model and Numerical Parameter Estimation." Mathematics 10, no. 23 (November 26, 2022): 4461. http://dx.doi.org/10.3390/math10234461.
Full textAbstract:
Iron is an essential element for brain metabolism. However, its imbalance and accumulation are implicated in the processes featuring neurodegenerative diseases, such as Alzheimer’s disease (AD). The brain barrier’s system maintains the sensitive homeostasis of iron in the brain. However, the impairment of the mechanisms of iron passage across the brain barrier is not clearly established. A mathematical model is proposed to macroscopically describe the iron exchange between blood and cerebral compartments. Numerical simulations are performed to reproduce biological values of iron levels in physiological and pathological conditions. Moreover, given different scenarios (neurological control and AD patients), a particle swarm optimization (PSO) algorithm is applied to estimate the parameters. This reverse work could be important to allow the understanding of the patient’s scenario. The presented mathematical model can therefore guide new experiments, highlighting further dysregulated mechanisms involved in neurodegeneration as well as the novel disease-modifying therapies counteracting the progression of neurodegenerative diseases.
21
Bulboaca, Adriana E., Sorana S. Bolboaca, Ioana C. Stanescu, Carmen A. Sfrangeu, and Angelo C. Bulboaca. "ANTIOXIDANT EFFECT OF FLAVONOIDS IN NEURODEGENERATIVE DISEASES." Romanian Journal of Neurology 16, no. 2 (June 30, 2017): 46–52. http://dx.doi.org/10.37897/rjn.2017.2.2.
Full textAbstract:
The investigation of the mechanisms that leads to neuronal apoptosis is under investigation all over the world. The enhancement of oxidative stress in brain neurons is one of the most important pathophysiological mechanism associated with neurodegeneration. The antioxidant effect of flavonoids can be one important mechanism for modulation of neuronal apoptosis in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In addition to their influence on the cerebral blood flow, flavonoids interact with signalization cascades that lead to the inhibition of neuronal death by oxidative stress apoptosis and thus promote neuronal survival and synaptic plasticity. Acting on the intracellular antioxidant mechanisms the flavonoids can become a balance regulator for production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Addition of antioxidant effect of flavonoids to dietary components can constitute an adjuvant therapy for delaying the neurodegenerative processes. The aim of this paper was to review the antioxidant effects of flavonoids in Alzheimer’s and Parkinson’s diseases.
22
Honjo, Kie, Sandra E. Black, and Nicolaas P. L. G. Verhoeff. "Alzheimer's Disease, Cerebrovascular Disease, and the β-amyloid Cascade." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 39, no. 6 (November 2012): 712–28. http://dx.doi.org/10.1017/s0317167100015547.
Full textAbstract:
Alzheimer's disease (AD), considered the commonest neurodegenerative cause of dementia, is associated with hallmark pathologies including extracellular amyloid-β protein (Aβ) deposition in extracellular senile plaques and vessels, and intraneuronal tau deposition as neurofibrillary tangles. Although AD is usually categorized as neurodegeneration distinct from cerebrovascular disease (CVD), studies have shown strong links between AD and CVD. There is evidence that vascular risk factors and CVD may accelerate Aβ 40-42 production/ aggregation/deposition and contribute to the pathology and symptomatology of AD. Aβ deposited along vessels also causes cerebral amyloid angiopathy. Amyloid imaging allowsin vivodetection of AD pathology, opening the way for prevention and early treatment, if disease-modifying therapies in the pipeline show safety and efficacy. In this review, we review the role of vascular factors and Aβ, underlining that vascular risk factor management may be important for AD prevention and treatment.
23
Kindler, Diana, Cinzia Maschio, Ruiqing Ni, Valerio Zerbi, Daniel Razansky, and Jan Klohs. "Arterial spin labeling demonstrates preserved regional cerebral blood flow in the P301L mouse model of tauopathy." Journal of Cerebral Blood Flow & Metabolism 42, no. 4 (November 25, 2021): 686–93. http://dx.doi.org/10.1177/0271678x211062274.
Full textAbstract:
There is growing evidence for the vascular contribution to cognitive impairment and dementia in Alzheimer’s disease (AD) and other neurodegenerative diseases. While perfusion deficits have been observed in patients with Alzheimer’s disease and tauopaties, little is known about the role of tau in vascular dysfunction. In the present study, regional cerebral blood (rCBF) was characterized in P301L mice with arterial spin labeling. No differences in rCBF in P301L mice compared to their age-matched non-transgenic littermates at mid (10–12 months of age) and advanced (19–21 months of age) disease stages. This was concomitant with preservation of cortical brain structure as assessed with structural T2-weighted magnetic resonance imaging. These results show that hypoperfusion and neurodegeneration are not a phenotype of P301L mice. More studies are thus needed to understand the relationship of tau, neurodegeneration and vascular dysfunction and its modulators in AD and primary tauopathies.
24
Pluta, Ryszard, Sławomir Januszewski, and Stanisław J. Czuczwar. "Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?" International Journal of Molecular Sciences 23, no. 12 (June 13, 2022): 6591. http://dx.doi.org/10.3390/ijms23126591.
Full textAbstract:
Currently, there is a lot of public interest in naturally occurring substances with medicinal properties that are minimally toxic, readily available and have an impact on health. Over the past decade, molecular hydrogen has gained the attention of both preclinical and clinical researchers. The death of pyramidal neurons in especially the CA1 area of the hippocampus, increased permeability of the blood-brain barrier, neuroinflammation, amyloid accumulation, tau protein dysfunction, brain atrophy, cognitive deficits and dementia are considered an integral part of the phenomena occurring during brain neurodegeneration after ischemia. This review focuses on assessing the current state of knowledge about the neuroprotective effects of molecular hydrogen following ischemic brain injury. Recent studies in animal models of focal or global cerebral ischemia and cerebral ischemia in humans suggest that hydrogen has pleiotropic neuroprotective properties. One potential mechanism explaining some of the general health benefits of using hydrogen is that it may prevent aging-related changes in cellular proteins such as amyloid and tau protein. We also present evidence that, following ischemia, hydrogen improves cognitive and neurological deficits and prevents or delays the onset of neurodegenerative changes in the brain. The available evidence suggests that molecular hydrogen has neuroprotective properties and may be a new therapeutic agent in the treatment of neurodegenerative diseases such as neurodegeneration following cerebral ischemia with progressive dementia. We also present the experimental and clinical evidence for the efficacy and safety of hydrogen use after cerebral ischemia. The therapeutic benefits of gas therapy open up new promising directions in breaking the translational barrier in the treatment of ischemic stroke.
25
Reesink, F. E., D. Vállez García, C. A. Sánchez-Catasús, D. E. Peretti, A. T. Willemsen, R. Boellaard, S. K. Meles, et al. "Crossed Cerebellar Diaschisis in Alzheimer’s Disease." Current Alzheimer Research 15, no. 13 (October 29, 2018): 1267–75. http://dx.doi.org/10.2174/1567205015666180913102615.
Full textAbstract:
Background: We describe the phenomenon of crossed cerebellar diaschisis (CCD) in four subjects diagnosed with Alzheimer’s disease (AD) according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with 18F-FDG PET and 11C-PiB PET imaging. Methods: 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease most prominent in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer delivery (a surrogate of relative cerebral blood flow) in the left hemisphere. CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. The mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The pathophysiology is thought to have a functional or reversible basis but can also reflect in secondary morphologic change. CCD is a well-recognized phenomenon, since the development of new imaging techniques, although scarcely described in neurodegenerative dementias. Results: To our knowledge this is the first report describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB PET imaging. CCD in our subjects was explained on a functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment. Conclusion: This suggests that CCD might be caused by non-amyloid neurodegeneration. The pathophysiological mechanism, clinical relevance and therapeutic implications of CCD and the role of the cerebellum in AD need further investigation.
26
Zhukova, I. A., V. M. Alifirova, and N. G. Zhukova. "Neurospecific enolase as a nonspecific neurodegenerative process marker." Bulletin of Siberian Medicine 10, no. 2 (April 28, 2011): 15–21. http://dx.doi.org/10.20538/1682-0363-2011-2-15-21.
Full textAbstract:
For the diagnosis and prognosis of various diseases is essential to determine specific markers in blood serum. Neuronspecific enolase (NSE) is a common marker of differentiatedneurons. The aim of the study was to evaluate the activity of NSE in patients with Parkinson's disease (PD) and chronic cerebral ischemia. The study results showed that the activity of NSE varied dependingon sex and age in PD patients, the stage and rate of progression of disease, age debut and severity of cognitive impairment. Thus, determination of NSE in the serum of PD patients should be included in the complex examination of patients with PD, as an additional marker of the neurodegenerative process.
27
Albert, Katrina, Jonna Niskanen, Sara Kälvälä, and Šárka Lehtonen. "Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia." International Journal of Molecular Sciences 22, no. 9 (April 21, 2021): 4334. http://dx.doi.org/10.3390/ijms22094334.
Full textAbstract:
Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.
28
Prikhodko, Veronika, Daria Chernyuk, Yurii Sysoev, Nikita Zernov, Sergey Okovityi, and Elena Popugaeva. "Potential Drug Candidates to Treat TRPC6 Channel Deficiencies in the Pathophysiology of Alzheimer’s Disease and Brain Ischemia." Cells 9, no. 11 (October 24, 2020): 2351. http://dx.doi.org/10.3390/cells9112351.
Full textAbstract:
Alzheimer’s disease and cerebral ischemia are among the many causative neurodegenerative diseases that lead to disabilities in the middle-aged and elderly population. There are no effective disease-preventing therapies for these pathologies. Recent in vitro and in vivo studies have revealed the TRPC6 channel to be a promising molecular target for the development of neuroprotective agents. TRPC6 channel is a non-selective cation plasma membrane channel that is permeable to Ca2+. Its Ca2+-dependent pharmacological effect is associated with the stabilization and protection of excitatory synapses. Downregulation as well as upregulation of TRPC6 channel functions have been observed in Alzheimer’s disease and brain ischemia models. Thus, in order to protect neurons from Alzheimer’s disease and cerebral ischemia, proper TRPC6 channels modulators have to be used. TRPC6 channels modulators are an emerging research field. New chemical structures modulating the activity of TRPC6 channels are being currently discovered. The recent publication of the cryo-EM structure of TRPC6 channels should speed up the discovery process even more. This review summarizes the currently available information about potential drug candidates that may be used as basic structures to develop selective, highly potent TRPC6 channel modulators to treat neurodegenerative disorders, such as Alzheimer’s disease and cerebral ischemia.
29
De Reuck, Jacques L., Vincent Deramecourt, Florent Auger, Nicolas Durieux, Charlotte Cordonnier, David Devos, Luc Defebvre, et al. "The Significance of Cortical Cerebellar Microbleeds and Microinfarcts in Neurodegenerative and Cerebrovascular Diseases." Cerebrovascular Diseases 39, no. 2 (2015): 138–43. http://dx.doi.org/10.1159/000371488.
Full textAbstract:
Background: As cortical microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases have been studied predominantly at the level of the cerebral hemispheres and linked to the presence of cerebral amyloid angiopathy (CAA), we aimed at determining with 7.0-tesla magnetic resonance imaging (MRI) whether the causes and the frequency of cortical cerebellar microbleeds (CCeMBs) and microinfarcts (CCeMIs) are the same. Materials and Methods: Hundred and four postmortem brains, composed of 29 with pure Alzheimer's disease (AD), 9 with AD associated to CAA, 10 with frontotemporal lobar degeneration, 9 with amyotrophic lateral sclerosis, 10 with Lewy body disease, 12 with progressive supranuclear palsy, 9 with vascular dementia (VaD), and 16 controls, were examined. On a horizontal section of a cerebellar hemisphere examined with 7.0-tesla MRI, the number CCeMBs and CCeMIs were compared between the different disease groups and the control group. The MRI findings were also compared with the corresponding mean values observed on histological examination of a separate standard horizontal section of a cerebellar hemisphere, used for diagnostic purpose. Results: CCeMBs and CCeMIs were only significantly increased in the VaD group. When comparing the diseased patients with and without CAA mutually and with those with arterial hypertension and severe atherosclerotic cerebrovascular disease, only in the latter an increase of CCeMBs and CCeMIs was observed. There was an excellent correlation between the MRI and the neuropathological findings. Conclusions: CCeMBs and CCeMIs are mainly due to atherosclerotic cerebrovascular disease and not due to CAA. Their increased presence cannot be included to the Boston diagnostic criteria for CAA.
30
Ryan, David K., Ville Karhunen, Bowen Su, Matthew Traylor, Tom G. Richardson, Stephen Burgess, Ioanna Tzoulaki, and Dipender Gill. "Genetic Evidence for Protective Effects of Angiotensin-Converting Enzyme Against Alzheimer Disease But Not Other Neurodegenerative Diseases in European Populations." Neurology Genetics 8, no. 5 (August 29, 2022): e200014. http://dx.doi.org/10.1212/nxg.0000000000200014.
Full textAbstract:
Background and ObjectivesAngiotensin-converting enzyme (ACE) inhibitors are a commonly prescribed class of medication used to treat heart failure, hypertension, and chronic kidney disease. However, previous observational studies have shown conflicting directions of associations between ACE inhibitors and risk of Alzheimer disease. Genetic evidence has supported a protective effect of cerebral ACE against Alzheimer disease (AD). However, it is unclear whether this effect is mediated through blood pressure and extends to other neurodegenerative diseases.MethodsWe performed genetic colocalization investigating an effect of cortical ACE expression on AD risk in people of European ancestry. We further investigated whether any effect of ACE expression on AD risk is mediated through changes in blood pressure and whether effects extend to Parkinson disease, small-vessel disease, or cognitive function in a Mendelian randomization paradigm.ResultsThere was genetic evidence supporting a protective effect of cortical ACE expression on AD risk in people of European ancestry. Although higher cortical ACE expression was associated with higher blood pressure, there was no strong evidence to support that its association with AD was mediated through blood pressure nor that ACE expression affected risk of other neurodegenerative traits.DiscussionGenetic evidence supports protective effects of cerebral ACE expression on AD, but not other neurodegenerative outcomes in people of European ancestry. Further work is required to investigate whether therapeutic inhibition of ACE increases risk of Alzheimer disease.
31
González, CA. "Introducing New Neurons in the Alzheimer’s Disease Brain." Journal of Stem Cells Research, Development & Therapy 7, no. 4 (December 31, 2021): 1–6. http://dx.doi.org/10.24966/srdt-2060/100080.
Full textAbstract:
Alzheimer’s disease is the most prevalent neurodegenerative disorder in the elderly population. The patients suffer cerebral atrophyas a consequence of extensive neuronal loss, especially in areas that play a role in memory and cognition. Cell therapies approaches have emerged as promising treatments to regenerate the brain tissue of the patients
32
Miller, John H., and Viswanath Das. "Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules." Current Pharmaceutical Design 26, no. 35 (October 16, 2020): 4362–72. http://dx.doi.org/10.2174/1381612826666200621171302.
Full textAbstract:
No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.
33
Maiti, Tanmoy Kumar, Subhas Konar, Shyamal Bir, Piyush Kalakoti, Papireddy Bollam, and Anil Nanda. "Role of apolipoprotein E polymorphism as a prognostic marker in traumatic brain injury and neurodegenerative disease: a critical review." Neurosurgical Focus 39, no. 5 (November 2015): E3. http://dx.doi.org/10.3171/2015.8.focus15329.
Full textAbstract:
OBJECT The difference in course and outcome of several neurodegenerative conditions and traumatic injuries of the nervous system points toward a possible role of genetic and environmental factors as prognostic markers. Apolipoprotein E (Apo-E), a key player in lipid metabolism, is recognized as one of the most powerful genetic risk factors for dementia and other neurodegenerative diseases. In this article, the current understanding of APOE polymorphism in various neurological disorders is discussed. METHODS The English literature was searched for various studies describing the role of APOE polymorphism as a prognostic marker in neurodegenerative diseases and traumatic brain injury. The wide ethnic distribution of APOE polymorphism was discussed, and the recent meta-analyses of role of APOE polymorphism in multiple diseases were analyzed and summarized in tabular form. RESULTS Results from the review of literature revealed that the distribution of APOE is varied in different ethnic populations. APOE polymorphism plays a significant role in pathogenesis of neurodegeneration, particularly in Alzheimer’s disease. APOE ε4 is considered a marker for poor prognosis in various diseases, but APOE ε2 rather than APOE ε4 has been associated with cerebral amyloid angiopathy-related bleeding and sporadic Parkinson’s disease. The role of APOE polymorphism in various neurological diseases has not been conclusively elucidated. CONCLUSIONS Apo-E is a biomarker for various neurological and systemic diseases. Therefore, while analyzing the role of APOE polymorphism in neurological diseases, the interpretation should be done after adjusting all the confounding factors. A continuous quest to look for associations with various neurological diseases and wide knowledge of available literature are required to improve the understanding of the role of APOE polymorphism in these conditions and identify potential therapeutic targets.
34
Holm-Mercer, Leah, Peter Rudge, Thomas Coysh, Sebastian Brandner, Zane Jaunmuktane, Haw raman Ramadan, Jo Ostler, Colin Smith, and Zita Reisz. "A novel neurodegenerative disease with multi-system features." Journal of Neurology, Neurosurgery & Psychiatry 93, no. 9 (August 12, 2022): e2.185. http://dx.doi.org/10.1136/jnnp-2022-abn2.39.
Full textAbstract:
Inherited prion diseases (IPD) are caused by mutations in the prion protein gene (PRNP) leading to accu- mulation of misfolded prion protein (PrP). Here we describe three novelPRNPmutations.A patient with gradually progressive cognitive decline, peripheral neuropathy, diarrhoea and autonomic dysfunction, starting in the 6th decade, whose father suffered a similar illness with neuropathology showing PrP-cerebral amyloid angiopathy, PrP-amyloid plaques and abundant tau disease with co-localising TDP-43, had a truncation mutation at codon 157.A missense mutation at codon 107 ofPRNPcausing an amino acid change from threonine to isoleucine was observed in a patient with a 9-year illness starting with cognitive decline followed by gait disturbance. Neuropathology shows multi-centric PrP-amyloid plaques.Substitution of proline to serine at codon 105 has previously been reported in one patient, however our case exhibited a different phenotype: dysphasia in the absence of neurological signs, with subsequent rapid cognitive then motor decline with myoclonus. Neuropathology showed predominantly synaptic deposition of PrP and sparse cerebellar plaques.These cases highlight the remarkable heterogeneity which can be seen within IPD, and the importance of genetic screening ofPRNPin cases where there is an unexplained phenotype, particularly when there is a family history.
35
Aulić, Suzana, Maria Laura Bolognesi, and Giuseppe Legname. "Small-Molecule Theranostic Probes: A Promising Future in Neurodegenerative Diseases." International Journal of Cell Biology 2013 (2013): 1–19. http://dx.doi.org/10.1155/2013/150952.
Full textAbstract:
Prion diseases are fatal neurodegenerative illnesses, which include Creutzfeldt-Jakob disease in humans and scrapie, chronic wasting disease, and bovine spongiform encephalopathy in animals. They are caused by unconventional infectious agents consisting primarily of misfolded, aggregated,β-sheet-rich isoforms, denoted prions, of the physiological cellular prion protein (PrPC). Many lines of evidence suggest that prions (PrPSc) act both as a template for this conversion and as a neurotoxic agent causing neuronal dysfunction and cell death. As such,PrPScmay be considered as both a neuropathological hallmark of the disease and a therapeutic target. Several diagnostic imaging probes have been developed to monitor cerebral amyloid lesions in patients with neurodegenerative disorders (such as Alzheimer’s disease, Parkinson’s disease, and prion disease). Examples of these probes are Congo red, thioflavin T, and their derivatives. We synthesized a series of styryl derivatives, denoted theranostics, and studied their therapeutic and/or diagnostic potentials. Here we review the salient traits of these small molecules that are able to detect and modulate aggregated forms of several proteins involved in protein misfolding diseases. We then highlight the importance of further studies for their practical implications in therapy and diagnostics.
36
EKTESSABI, A. M., S. FUJISAWA, K. TAKADA, K. YOSHIDA, H. MURAYAMA, and R. W. SHIN. "ANALYSIS OF THE BRAIN TISSUES FROM A PATIENT WITH ALZHEIMER'S DISEASE AND EFFECTS OF CHELATING TREATMENT." International Journal of PIXE 09, no. 03n04 (January 1999): 297–303. http://dx.doi.org/10.1142/s0129083599000395.
Full textAbstract:
Alzheimer's, Parkinson's disease and ALS are among major neurodegenerative diseases. The cause of neurodegeneration is unknown, but there are indications that excessive accumulation of essential elements, and sometimes, incorporation of toxic foreign elements in neurons aggravate neurodegeneration. During the past decade, many researchers investigated the causative factors in degenerative diseases to specify genetic or environmental factor. PIXE analysis has been used for these studies because of the sample preparation is easy and detection limit is very low. However, the concentration of matrix elements and foreign elements are extremely low and difficult to detect and to quantify. In this study, specimens from patients with Alzheimer's disease with no chemical treatment, and those with chelating were analyzed. In all analyzed specimens, Na , Al , Si , P , S , Cl , Ca , Ti , V , Cr , Fe and Cu were detected. Each specimen in this study consisted of cerebral cortex and substantia alba. From these experiments we can observe a clear tendency that the accumulation of the metal elements are different depending on the constituent tissues, and the method of sample preparation has a dominant role in the measurement results.
37
Serwach, Karolina, and Joanna Gruszczynska-Biegala. "STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases." International Journal of Molecular Sciences 20, no. 9 (May 9, 2019): 2289. http://dx.doi.org/10.3390/ijms20092289.
Full textAbstract:
Neuronal calcium (Ca2+) influx has long been ascribed mainly to voltage-gated Ca2+ channels and glutamate receptor channels. Recent research has shown that it is also complemented by stromal interaction molecule (STIM) protein-mediated store-operated Ca2+ entry (SOCE). SOCE is described as Ca2+ flow into cells in response to the depletion of endoplasmic reticulum Ca2+ stores. The present review summarizes recent studies that indicate a relationship between neuronal SOCE that is mediated by STIM1 and STIM2 proteins and glutamate receptors under both physiological and pathological conditions, such as neurodegenerative disorders. We present evidence that the dysregulation of neuronal SOCE and glutamate receptor activity are hallmarks of acute neurodegenerative diseases (e.g., traumatic brain injury and cerebral ischemia) and chronic neurodegenerative diseases (e.g., Alzheimer’s disease and Huntington’s disease). Emerging evidence indicates a role for STIM proteins and glutamate receptors in neuronal physiology and pathology, making them potential therapeutic targets.
38
Bennett, C. Frank, Holly B. Kordasiewicz, and Don W. Cleveland. "Antisense Drugs Make Sense for Neurological Diseases." Annual Review of Pharmacology and Toxicology 61, no. 1 (January 6, 2021): 831–52. http://dx.doi.org/10.1146/annurev-pharmtox-010919-023738.
Full textAbstract:
The genetic basis for most inherited neurodegenerative diseases has been identified, yet there are limited disease-modifying therapies for these patients. A new class of drugs—antisense oligonucleotides (ASOs)—show promise as a therapeutic platform for treating neurological diseases. ASOs are designed to bind to the RNAs either by promoting degradation of the targeted RNA or by elevating expression by RNA splicing. Intrathecal injection into the cerebral spinal fluid results in broad distribution of antisense drugs and long-term effects. Approval of nusinersen in 2016 demonstrated that effective treatments for neurodegenerative diseases can be identified and that treatments not only slow disease progression but also improve some symptoms. Antisense drugs are currently in development for amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, and Angelman syndrome, and several drugs are in late-stage research for additional neurological diseases. This review highlights the advances in antisense technology as potential treatments for neurological diseases.
39
Agbangla, Fraser, and Albinet. "An Overview of the Cardiorespiratory Hypothesis and Its Potential Contribution to the Care of Neurodegenerative Disease in Africa." Medicina 55, no. 9 (September 17, 2019): 601. http://dx.doi.org/10.3390/medicina55090601.
Full textAbstract:
One hypothesis that could explain the beneficial effects of physical exercise on cognitive function is the cardiorespiratory hypothesis. This hypothesis proposes that improved cognitive functioning may be in part a result of the physiological processes that occur after physical exercise such as: Increased cerebral perfusion and regional cerebral blood flow. These processes ensure increased oxygenation and glucose transportation to the brain, which together can improve cognitive function. The objective of this narrative review is to examine the contribution of this hypothesis in the care of African older adults with neurodegenerative conditions (i.e., dementia (Alzheimer’s disease)) or with mild cognitive impairments. Although studies in developed countries have examined people of African descent (i.e., with African Americans), only the limited findings presented in this review reflect how these conditions are also important for the African continent. This review revealed that no studies have examined the effects of cardiorespiratory fitness on neurodegenerative disease in Africa. African nations, like many other developing countries, have an aging population that is growing and will face an increased risk of neurodegenerative declines. It is therefore imperative that new research projects be developed to explore the role of the cardiorespiratory fitness in neurodegenerative disease prevention in African nations.
40
Abe, Koji, Toru Yamashita, Shunya Takizawa, Satoshi Kuroda, Hiroyuki Kinouchi, and Nobutaka Kawahara. "Stem Cell Therapy for Cerebral Ischemia: From Basic Science to Clinical Applications." Journal of Cerebral Blood Flow & Metabolism 32, no. 7 (January 18, 2012): 1317–31. http://dx.doi.org/10.1038/jcbfm.2011.187.
Full textAbstract:
Recent stem cell technology provides a strong therapeutic potential not only for acute ischemic stroke but also for chronic progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis with neuroregenerative neural cell replenishment and replacement. In addition to resident neural stem cell activation in the brain by neurotrophic factors, bone marrow stem cells (BMSCs) can be mobilized by granulocyte-colony stimulating factor for homing into the brain for both neurorepair and neuroregeneration in acute stroke and neurodegenerative diseases in both basic science and clinical settings. Exogenous stem cell transplantation is also emerging into a clinical scene from bench side experiments. Early clinical trials of intravenous transplantation of autologous BMSCs are showing safe and effective results in stroke patients. Further basic sciences of stem cell therapy on a neurovascular unit and neuroregeneration, and further clinical advancements on scaffold technology for supporting stem cells and stem cell tracking technology such as magnetic resonance imaging, single photon emission tomography or optical imaging with near-infrared could allow stem cell therapy to be applied in daily clinical applications in the near future.
41
Yang, Xinwang, Ying Wang, Chunyun Wu, and Eng-Ang Ling. "Animal Venom Peptides as a Treasure Trove for New Therapeutics Against Neurodegenerative Disorders." Current Medicinal Chemistry 26, no. 25 (October 16, 2019): 4749–74. http://dx.doi.org/10.2174/0929867325666181031122438.
Full textAbstract:
Background:Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and cerebral ischemic stroke, impose enormous socio-economic burdens on both patients and health-care systems. However, drugs targeting these diseases remain unsatisfactory, and hence there is an urgent need for the development of novel and potent drug candidates.Methods:Animal toxins exhibit rich diversity in both proteins and peptides, which play vital roles in biomedical drug development. As a molecular tool, animal toxin peptides have not only helped clarify many critical physiological processes but also led to the discovery of novel drugs and clinical therapeutics.Results:Recently, toxin peptides identified from venomous animals, e.g. exenatide, ziconotide, Hi1a, and PcTx1 from spider venom, have been shown to block specific ion channels, alleviate inflammation, decrease protein aggregates, regulate glutamate and neurotransmitter levels, and increase neuroprotective factors.Conclusion:Thus, components of venom hold considerable capacity as drug candidates for the alleviation or reduction of neurodegeneration. This review highlights studies evaluating different animal toxins, especially peptides, as promising therapeutic tools for the treatment of different neurodegenerative diseases and disorders.
42
Pellegrini, Marco, Aldo Vagge, Lorenzo Ferro Desideri, Federico Bernabei, Giacinto Triolo, Rodolfo Mastropasqua, Chiara Del Noce, et al. "Optical Coherence Tomography Angiography in Neurodegenerative Disorders." Journal of Clinical Medicine 9, no. 6 (June 2, 2020): 1706. http://dx.doi.org/10.3390/jcm9061706.
Full textAbstract:
Retinal microcirculation shares similar features with cerebral small blood vessels. Thus, the retina may be considered an accessible ‘window’ to detect the microvascular damage occurring in the setting of neurodegenerative disorders. Optical coherence tomography angiography (OCT-A) is a non-invasive imaging modality providing depth resolved images of blood flow in the retina, choroid, and optic nerve. In this review, we summarize the current literature on the application of OCT-A in glaucoma and central nervous system conditions such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Future directions aiming at evaluating whether OCT-A can be an additional biomarker for the early diagnosis and monitoring of neurodegenerative disorders are also discussed.
43
Salazar, Kenneth, and Caleb Salazar Hernández. "PENFIGOIDE AMPOLLAR Y SU ASOCIACIÓN CON TRASTORNOS NEURODEGENERATIVOS. Reporte de 4 casos en la región Occidente de Costa Rica." Revista de la Facultad de Medicina de la Universidad de lberoamérica 1, no. 1 (January 1, 2023): 25–35. http://dx.doi.org/10.54376/rcmui.v1i1.103.
Full textAbstract:
RESUMEN
El Penfigoide ampollar es una enfermedad de tipo autoinmune que se origina por la producción de autoanticuerpos contra diferentes componentes de la membrana basal. El penfigoide ampollar se vincula con padecimientos crónicos como diabetes mellitus, neoplasias, trastornos psiquiátricos o neurodegenerativos como el accidente cerebrovascular, la isquemia cerebral transitoria, la enfermedad de Parkinson y la enfermedad de Alzheimer entre otras.
Se presenta una serie de 4 casos cuyos hallazgos clínicos e histopatológicos corresponden a penfigoide ampollar los cuales mostraron algún grado de déficit neurológico.
SUMMARY
Bullous pemphigoid is an autoimmune bullous disease caused by the production of autoantibodies against different components of the basement membrane. It is associated with chronic conditions such as diabetes mellitus, neoplasms, psychiatric or neurodegenerative disorders such as stroke, transient cerebral ischemia, Parkinson's disease, Alzheimer's disease among others.
A series of 4 cases is presented whose clinical and histopathological findings correspond to bullous pemphigoid which showed some degree of neurological deficit.
44
Ohta, Emiko, and Yoshihisa Takiyama. "MRI Findings in Neuroferritinopathy." Neurology Research International 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/197438.
Full textAbstract:
Neuroferritinopathy is a neurodegenerative disease which demonstrates brain iron accumulation caused by the mutations in the ferritin light chain gene. On brain MRI in neuroferritinopathy, iron deposits are observed as low-intensity areas on T2WI and as signal loss on T2*WI. On T2WI, hyperintense abnormalities reflecting tissue edema and gliosis are also seen. Another characteristic finding is the presence of symmetrical cystic changes in the basal ganglia, which are seen in the advanced stages of this disorder. Atrophy is sometimes noted in the cerebellar and cerebral cortices. The variety in the MRI findings is specific to neuroferritinopathy. Based on observations of an excessive iron content in patients with chronic neurologic disorders, such as Parkinson disease and Alzheimer disease, the presence of excess iron is therefore recognized as a major risk factor for neurodegenerative diseases. The future development of multimodal and advanced MRI techniques is thus expected to play an important role in accurately measuring the brain iron content and thereby further elucidating the neurodegenerative process.
45
Goldeck, David, Claudia Schulte, Marcia Cristina Teixeira dos Santos, Dieter Scheller, Lilly Öttinger, Graham Pawelec, Christian Deuschle, Daniela Berg, Andre Nogueira da Costa, and Walter Maetzler. "Higher Frequencies of T-Cells Expressing NK-Cell Markers and Chemokine Receptors in Parkinson’s Disease." Journal of Ageing and Longevity 3, no. 1 (December 22, 2022): 1–10. http://dx.doi.org/10.3390/jal3010001.
Full textAbstract:
Immune cells are thought to be involved in a destructive cycle of sterile cerebral inflammatory responses in neurodegenerative diseases such as Parkinson’s Disease (PD). Despite their peripheral origin, immune cells may enter the CNS due to impaired blood–brain barrier function and may potentially contribute to neuronal damage. Hence, specific characteristics of peripherally activated immune cells could help in understanding neurodegeneration in PD and could potentially serve as accessible disease markers. To investigate immune cell activation status, the expression of receptors for cell surface molecules CD161, NKG2A, NKG2C and NKG2D as well as chemokine receptors CCR6, CXCR2, CXCR3 and CCR5 associated with neurodegenerative diseases was investigated. The frequencies of peripheral CD8+ T-cells expressing the inhibitory and activating receptors NKG2A and NKG2C, and the activating receptor NKG2D were higher in PD patients than in healthy matched controls. The frequencies of NKG2C+CD8− cells were also higher, whereas the frequencies of CD161+ cells were not significantly different. Of the chemokine receptor-expressing cells, only the proportion of CD4−CD56+CCR5+ T-cells was higher in PD patients than in the controls. These observations support the hypothesis that an imbalance in the activation state of T-cells plays a role in the pathological processes of PD and suggest that peripheral blood immune cell phenotypes could be specific early markers for inflammation in PD.
46
Sobański, Michał, Anna Zacharzewska-Gondek, Marta Waliszewska-Prosół, Marek Jan Sąsiadek, Anna Zimny, and Joanna Bladowska. "A Review of Neuroimaging in Rare Neurodegenerative Diseases." Dementia and Geriatric Cognitive Disorders 49, no. 6 (2020): 544–56. http://dx.doi.org/10.1159/000512543.
Full textAbstract:
<b><i>Purpose:</i></b> Due to the variety of clinical symptoms that occur in rare neurodegenerative diseases and difficulties in the correct diagnosis, there is a need to learn their characteristic imaging findings by using conventional MRI. That knowledge helps to determine the appropriate differential diagnosis and avoid misdiagnosis. The aim of this review is to present the typical neuroimaging signs of the selected neurodegenerative disorders and to create a practical approach to imaging findings useful in everyday clinical practice. <b><i>Images:</i></b> Images of progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), Creutzfeldt-Jakob disease (CJD), Wilson’s disease (WD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are provided to visualize and distinguish the typical features of those diseases and therefore to assist neurologists and neuroradiologists in decision-making process. <b><i>Conclusions:</i></b> It is important to know the characteristic MRI features of rare neurodegenerative diseases and to use them in everyday clinical practice. MRI is a valuable tool when considering the initial diagnosis because it is proven to be very useful in the differentiation of more advanced stages of the rare neurodegenerative diseases but also from other neurodegenerative disorders.
47
Hosoi, Toru, and Koichiro Ozawa. "Endoplasmic reticulum stress in disease: mechanisms and therapeutic opportunities." Clinical Science 118, no. 1 (September 28, 2009): 19–29. http://dx.doi.org/10.1042/cs20080680.
Full textAbstract:
Various stresses, which impair ER (endoplasmic reticulum) function, lead to an accumulation of unfolded or misfolded proteins. ER stress triggers many rescuer responses, including a UPR (unfolded protein response). Increasing evidence has suggested that ER stress is involved in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and cerebral ischaemic insults), cancer, obesity and diabetes. In the present review, we consider the importance of ER stress under pathological conditions in mammals. Furthermore, we discuss the therapeutic potential for treatment targeting ER stress.
48
De Reuck, Jacques L. "Post-mortem Magnetic Resonance Imaging as an Additional Tool of the Neuropathological Examination of Neurodegenerative and Cerebrovascular Diseases." European Neurological Review 11, no. 1 (2016): 22. http://dx.doi.org/10.17925/enr.2016.11.01.22.
Full textAbstract:
Neuropathological examination of post-mortem brains of patients with dementia due to neurodegenerative and cerebrovascular changes remains important, as the family wants to be sure about the clinical diagnosis and the risk of a hereditary disease. 7.0-tesla magnetic resonance imaging (MRI) can be applied as an additional tool to examine post-mortem brains of patients with neurodegenerative and cerebrovasular diseases. It allows examination of serial coronal sections of a cerebral hemisphere and horizontal sections of brainstem and cerebellum and comparison with the neuropathological lesions. Post-mortem MRI can show the degree and the distribution of the cerebral atrophy. Additional small cerebrovascular lesions can be quantified. The degree of iron load, not due to microbleeds, can be evaluated in different basal ganglia and brainstem structures. Three to six serial sections of a cerebral hemisphere and one section of brainstem and cerebellum allow the evaluation of the most important brain changes and to select the small samples to be used for histological diagnostic purposes. These correlation studies are extremely important for the future, when more 7.0-tesla MRI machines will be available forin vivoclinical-radiological diagnosis. This article is a review of post-mortem MRI data in the brains of patients with neurodegenerative and vascular dementias.
49
Shibuya, Mika, Claudia da Costa Leite, and Leandro Tavares Lucato. "Neuroimaging in cerebral small vessel disease: Update and new concepts." Dementia & Neuropsychologia 11, no. 4 (December 2017): 336–42. http://dx.doi.org/10.1590/1980-57642016dn11-040002.
Full textAbstract:
ABSTRACT. In recent years, small vessel disease (SVD) has been recognized for its major impact on cognitive impairment in elderly people, where it is often difficult to separate its effects from those of neurodegenerative diseases individually. SVD is a systemic disease, probably related to diffuse endothelial dysfunction, which affects the perforating arterioles, capillaries and venules in the brain. Although often asymptomatic, it is responsible for almost half of all dementia cases and a significant proportion of stroke cases. Imaging features found on magnetic resonance include recent small subcortical infarctions, lacunes of presumed vascular origin, white matter hyperintensity of presumed vascular origin, prominent perivascular spaces and cerebral microbleeds. The recognition of these imaging findings as a spectrum of the same disease caused by endothelial dysfunction of small cerebral vessels can allow an overall analysis of the disease and thus the development of more effective preventive and therapeutic strategies.
50
Soto-Rojas, Luis O., Mar Pacheco-Herrero, Paola A. Martínez-Gómez, B. Berenice Campa-Córdoba, Ricardo Apátiga-Pérez, Marcos M. Villegas-Rojas, Charles R. Harrington, Fidel de la Cruz, Linda Garcés-Ramírez, and José Luna-Muñoz. "The Neurovascular Unit Dysfunction in Alzheimer’s Disease." International Journal of Molecular Sciences 22, no. 4 (February 18, 2021): 2022. http://dx.doi.org/10.3390/ijms22042022.
Full textAbstract:
Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.