Academic literature on the topic 'Protein deposition disease'
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Journal articles on the topic "Protein deposition disease"
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Kaytor, Michael D., and Stephen T. Warren. "Aberrant Protein Deposition and Neurological Disease." Journal of Biological Chemistry 274, no. 53 (December 31, 1999): 37507–10. http://dx.doi.org/10.1074/jbc.274.53.37507.
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Leung, Nelson, Maria E. Drosou, and Samih H. Nasr. "Dysproteinemias and Glomerular Disease." Clinical Journal of the American Society of Nephrology 13, no. 1 (November 7, 2017): 128–39. http://dx.doi.org/10.2215/cjn.00560117.
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Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein–related kidney diseases.
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Haapasalo, Annakaisa, Jayashree Viswanathan, Lars Bertram, Hilkka Soininen, Rudolph E. Tanzi, and Mikko Hiltunen. "Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation." Biochemical Society Transactions 38, no. 1 (January 19, 2010): 150–55. http://dx.doi.org/10.1042/bst0380150.
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Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin–proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of Aβ (amyloid β-peptide) in the brain. Evidence shows that the AD-associated PS (presenilin) also forms aggregates under certain conditions and that another AD-associated protein, ubiquilin-1, controls protein aggregation and deposition of aggregated proteins. Here, we review the current knowledge of ubiquilin-1 and PS in protein aggregation and related events that potentially influence neurodegeneration.
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Deret, S., J. Chomilier, D. B. Huang, J. L. Preud'homme, F. J. Stevens, and P. Aucouturier. "Molecular modeling of immunoglobulin light chains implicates hydrophobic residues in non-amyloid light chain deposition disease." Protein Engineering Design and Selection 10, no. 10 (October 1, 1997): 1191–97. http://dx.doi.org/10.1093/protein/10.10.1191.
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Samimi, Nastaran, Akiko Asada, and Kanae Ando. "Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle." Galen Medical Journal 9 (January 27, 2020): 1681. http://dx.doi.org/10.31661/gmj.v9i0.1681.
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Abnormal deposition of misfolded proteins is a neuropathological characteristic shared by many neurodegenerative disorders including Alzheimer’s disease (AD). Generation of excessive amounts of aggregated proteins and impairment of degradation systems for misfolded proteins such as autophagy can lead to accumulation of proteins in diseased neurons. Molecules that contribute to both these effects are emerging as critical players in disease pathogenesis. Furthermore, impairment of autophagy under disease conditions can be both a cause and a consequence of abnormal protein accumulation. Specifically, disease-causing proteins can impair autophagy, which further enhances the accumulation of abnormal proteins. In this short review, we focus on the relationship between the microtubule-associated protein tau and autophagy to highlight a feed-forward mechanism in disease pathogenesis. [GMJ.2020;9:e1681]
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Crestini, Alessio, Francesca Santilli, Stefano Martellucci, Elena Carbone, Maurizio Sorice, Paola Piscopo, and Vincenzo Mattei. "Prions and Neurodegenerative Diseases: A Focus on Alzheimer’s Disease." Journal of Alzheimer's Disease 85, no. 2 (January 18, 2022): 503–18. http://dx.doi.org/10.3233/jad-215171.
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Specific protein misfolding and aggregation are mechanisms underlying various neurodegenerative diseases such as prion disease and Alzheimer’s disease (AD). The misfolded proteins are involved in prions, amyloid-β (Aβ), tau, and α-synuclein disorders; they share common structural, biological, and biochemical characteristics, as well as similar mechanisms of aggregation and self-propagation. Pathological features of AD include the appearance of plaques consisting of deposition of protein Aβ and neurofibrillary tangles formed by the hyperphosphorylated tau protein. Although it is not clear how protein aggregation leads to AD, we are learning that the cellular prion protein (PrPC) plays an important role in the pathogenesis of AD. Herein, we first examined the pathogenesis of prion and AD with a focus on the contribution of PrPC to the development of AD. We analyzed the mechanisms that lead to the formation of a high affinity bond between Aβ oligomers (AβOs) and PrPC. Also, we studied the role of PrPC as an AβO receptor that initiates an AβO-induced signal cascade involving mGluR5, Fyn, Pyk2, and eEF2K linking Aβ and tau pathologies, resulting in the death of neurons in the central nervous system. Finally, we have described how the PrPC-AβOs interaction can be used as a new potential therapeutic target for the treatment of PrPC-dependent AD.
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Nalbantoglu, Josephine. "β-Amyloid Protein in Alzheimer's Disease." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 18, S3 (August 1991): 424–27. http://dx.doi.org/10.1017/s0317167100032595.
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ABSTRACT:β-amyloid protein, a 42-43 amino acid polypeptide, accumulates abnormally in senile plaques and the cerebral vasculature in Alzheimer's disease. This polypeptide is derived from a membrane-associated precursor which has several isoforms expressed in many tissues. The precursor protein is processed constitutively within the P-amyloid domain, leading to the release of the large β-terminal portion into the extracellular medium, β-amyloid protein may be toxic to certain neuronal cell types and its early deposition may be an important event in the pathogenesis of Alzheimer's disease.
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Boldueva, Svetlana A., Dmitriy S. Evdokimov, Natalia S. Shvets, Anahit V. Shahbazyan, Elena Yu Kalinina, and Lyubov B. Mitrofanova. "Systemic transtiretin amyloidosis in the elderly patient with recurrent pleural effusions." HERALD of North-Western State Medical University named after I.I. Mechnikov 13, no. 3 (October 15, 2021): 91–98. http://dx.doi.org/10.17816/mechnikov79512.
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Systemic amyloidosis is a group of diseases associated with extracellular deposition of fibrillar proteins, which leads to a loss of normal organ structure and function. Transthyretin amyloidosis occurs with the deposition of amyloid, consisting of transthyretin transport protein, and can be a genetic or degenerative disease of senility (acquired from the deposition of wild-type transthyretin).
The article describes the clinical case of transthyretine amyloidosis in elderly patient, manifested by recurrent pleural effusions and biventricular heart failure demonstrating the complexity of timely diagnosis of wild-type transthyretin amyloidosis.
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Thorp, K. E., James A. Thorp, Elise M. Thorp, Margery M. Thorp, and Paul R. Walker. "COVID-19: Energy, Protein Folding & Prion Disease." Gazette of Medical Sciences 3, no. 1 (September 13, 2022): 179–206. http://dx.doi.org/10.46766/thegms.neuro.22083101.
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The recent recognition of intravascular amyloid formation with deposition of insoluble microthrombi throughout the circulatory system in primary COVID-19 infection or following administration of mRNA vaccines is a pivotal discovery that alters conventional notions about the nature of the underlying pathologic process at play in SARS-CoV-2 infection.
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Mold, Matthew John, Adam O’Farrell, Benjamin Morris, and Christopher Exley. "Aluminum and Neurofibrillary Tangle Co-Localization in Familial Alzheimer’s Disease and Related Neurological Disorders." Journal of Alzheimer's Disease 78, no. 1 (October 27, 2020): 139–49. http://dx.doi.org/10.3233/jad-200838.
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Background: Protein misfolding disorders are frequently implicated in neurodegenerative conditions. Familial Alzheimer’s disease (fAD) is an early-onset and aggressive form of Alzheimer’s disease (AD), driven through autosomal dominant mutations in genes encoding the amyloid precursor protein and presenilins 1 and 2. The incidence of epilepsy is higher in AD patients with shared neuropathological hallmarks in both disease states, including the formation of neurofibrillary tangles. Similarly, in Parkinson’s disease, dementia onset is known to follow neurofibrillary tangle deposition. Objective: Human exposure to aluminum has been linked to the etiology of neurodegenerative conditions and recent studies have demonstrated a high level of co-localization between amyloid-β and aluminum in fAD. In contrast, in a donor exposed to high levels of aluminum later developing late-onset epilepsy, aluminum and neurofibrillary tangles were found to deposit independently. Herein, we sought to identify aluminum and neurofibrillary tangles in fAD, Parkinson’s disease, and epilepsy donors. Methods: Aluminum-specific fluorescence microscopy was used to identify aluminum in neurofibrillary tangles in human brain tissue. Results: We observed aluminum and neurofibrillary-like tangles in identical cells in all respective disease states. Co-deposition varied across brain regions, with aluminum and neurofibrillary tangles depositing in different cellular locations of the same cell. Conclusion: Neurofibrillary tangle deposition closely follows cognitive-decline, and in epilepsy, tau phosphorylation associates with increased mossy fiber sprouting and seizure onset. Therefore, the presence of aluminum in these cells may exacerbate the accumulation and misfolding of amyloidogenic proteins including hyperphosphorylated tau in fAD, epilepsy, and Parkinson’s disease.
Dissertations / Theses on the topic "Protein deposition disease"
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Cairns, Nigel John. "Beta-amyloid protein deposition in the brain and its role in the pathogenesis of Alzheimer's disease." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283135.
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Marshall, Jeffrey Richard. "Kinetics of Aβ Peptide Deposition: Toward In Vivo Imaging of Alzheimer’s Disease Amyloid." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1021389976.
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Horton, Katherine. "The anatomical distribution of B-amyloid protein in the brain : do neurodevelopmental abnormalities of surgical intervention affect the pattern of deposition." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281748.
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Maesako, Masato. "Exercise is more effective than diet control in preventing high fat diet-induced β-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188709.
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Munishkina, Larissa. "[alpha]-synuclein, its properties and connection to protein deposition diseases /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2004. http://uclibs.org/PID/11984.
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Moulinet, Inès. "Vers une meilleure compréhension des facteurs psychoaffectifs (anxiété et dépression) dans le vieillissement normal et pathologique : liens avec la cognition et la neuroimagerie multimodale Sex-specificities in anxiety and depressive symptoms across the lifespan and their links with multimodal neuroimaging Relationships of depressive symptoms to brain markers of neurodegeneration and amyloid deposition across the Alzheimer’s continuum Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMC422.
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Les symptômes psychoaffectifs anxieux et dépressifs infra-cliniques sont fréquents chez les personnes âgées et sont associés à un risque accru de développer une démence et de progresser d’un stade prédémentiel à un stade démentiel. Cependant, ils pourraient également être des symptômes associés à une démence, et pourraient constituer une manifestation clinique de la pathologie sous-jacente. L’objectif de cette thèse était de contribuer à une meilleure compréhension des liens entre symptômes anxieux et dépressifs et les modifications cognitives et cérébrales structurales, fonctionnelles et moléculaires typiques de la maladie d’Alzheimer (MA), à la fois dans le vieillissement normal et au cours de cette pathologie. Nos résultats montrent que des symptômes anxieux élevés sont associés à un volume de substance grise plus bas chez les sujets âgés cognitivement sains, et ce uniquement chez les femmes. Cette même association est présente chez les sujets Subjective Cognitive Decline (SCD) recrutés dans la population générale, et montre une vulnérabilité accrue aux maladies neurodégénératives liées à l’âge, telles que les démences. Chez les SCD ayant consulté pour leur déclin cognitif subjectif, des symptômes dépressifs élevés sont associés à une charge amyloïde plus importante dans le cerveau, et donc à un risque accru de développer une MA, tandis que chez les sujets Mild Cognitive Impairment (MCI) et MA amyloïde positifs, ils sont liés à une meilleure cognition et conscience de ses propres troubles. Les symptômes psychoaffectifs semblent donc avoir un rôle évolutif au cours du passage du vieillissement normal au vieillissement pathologique, d’abord manifestation d’une vulnérabilité cérébrale, puis manifestation d’une pathologie sous-jacente et d’un risque de développement de MA, ils sont au contraire un marqueur de préservation chez les patients présentant un déclin cognitif (MCI et MA)Subclinical psychoaffective symptoms of anxiety and depression are common in the elderly and are associated with an increased risk of developing dementia and progressing from a pre-dementia stage to a dementia stage. However, they could also be symptoms associated with dementia and could be a clinical manifestation of the underlying pathology. The aim of this thesis was to contribute towards a better understanding of the links between anxiety and depressive symptoms and Alzheimer's disease (AD) hallmarks, including cognitive, structural, functional and molecular modifications, both in normal aging and during the course of this pathology. Our results show that higher anxiety symptoms are associated with lower grey matter volume in cognitively healthy elderly subjects, but only in women. This same association is present in all Subjective Cognitive Decline (SCD) participants recruited from the general population, and shows an increased vulnerability to age-related neurodegenerative diseases such as dementia. In Subjective Cognitive Decline (SCD) subjects, high depressive symptoms are associated with greater amyloid load in the brain, and thus an increased risk of developing AD, while in amyloid-positive Mild Cognitive Impairment (MCI) and AD subjects, they are related to better cognition and awareness of their cognitive deficits. Psychoaffective symptoms thus seem to have an evolving role during the transition from normal aging to pathological aging; they first manifest a brain vulnerability, then an underlying pathology and a risk of developing AD, and then are a marker of preservation in patients with cognitive decline (MCI and AD)
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MANNINI, BENEDETTA. "Early-forming aberrant aggregates in protein deposition diseases: structural characteristics, interaction with molecular chaperones, ability to trigger inflammation." Doctoral thesis, 2013. http://hdl.handle.net/2158/806710.
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Protein aggregation into amyloid fibrils is the hallmark of many human pathologies, including Alzheimer's disease and Parkinson's disease. The aberrant assembly of peptides and proteins into fibrillar aggregates proceeds through oligomeric intermediates thought to be the primary pathogenic species in many of these protein deposition diseases. Since the first year of my PhD, I have been studying protein aggregation, focusing on misfolded protein oligomers formed by the N-terminal domain of the bacterial HypF protein from E. coli (HypF-N). These oligomers are a useful model system in the context of disease-associated protein aggregation because they have the same properties as the disease-related ones and are highly stable, allowing a detailed structural and functional investigation. Moreover, under two different conditions, HypF-N aggregates into two types of oligomers characterized by an opposite biological activity, since only one is toxic whereas the other is benign to cultured cells, facilitating the utilization of appropriate control nontoxic oligomers in our experiments.
In Chapter 2, the first one describing results in my thesis, the toxicity of HypF-N oligomers, as well as the aggregates formed by the amyloid-β peptide and the islet amyloid polypeptide, was tested in the presence of molecular chaperones, namely αB-crystallin, Hsp70, clusterin, α2-macroglobulin and haptoglobin. Molecular chaperones play a pivotal role in the regulation of the proteome homeostasis, as they facilitate protein folding, inhibit protein aggregation, disaggregate pre-formed assemblies and promote clearance of misfolded aggregates. In this chapter we show that molecular chaperones also affect the structure and toxicity of protein misfolded oligomers. Indeed, measures of the cell viability showed that all the five chaperones are effective in suppressing the toxicity of oligomers formed by all three proteins. Infrared spectroscopy and site-directed labeling experiments using pyrene ruled out a structural reorganization within the discrete HypF-N oligomers, even at the amino acid residue level. By contrast, analysis performed using confocal microscopy, SDS-PAGE and intrinsic fluorescence measurements revealed binding between the oligomers and the chaperones; atomic force microscopy (AFM) imaging indicated that large assemblies of oligomers are formed in the presence of the chaperones. This suggests that the chaperones bind to the oligomers and promote their assembly into larger species, with consequent decrease in their diffusional mobility and burial of hydrophobic surface.
In Chapter 3, with the aim of identifying the structural determinants responsible for the toxicity of misfolded oligomers, we created a set of HypF-N oligomeric variants by replacing one or more charged aminoacids with apolar aminoacids into the sequence of the wt protein, and allowing the mutated proteins to aggregate under different conditions. The resulting oligomeric species were characterized by different levels of cytotoxicity, as assessed by measurements of MTT reduction, tests with the apoptotic marker Hoechst and measurements of Ca2+ influx. The structural properties of the oligomeric variants was performed by evaluating the exposure of their hydrophobic surfaces to the solvent with ANS binding and by measuring their size by means of turbidimetry and light scattering measurements. A significant correlation was found between ANS binding and size of the oligomers, indicating that an increase of surface hydrophobicity causes an increase of the size of the oligomers. Moreover, both superficial hydrophobicity and size were found to influence the oligomer biological activity, cooperating in determining the levels of toxicity of the aggregates.
In Chapter 4, we used HypF-N toxic misfolded oligomers to investigate their interactions with transthyretin (TTR). This protein is a homotetrameric protein which can disassemble into its monomers, misfold and aggregate into fibrils whose growth is considered the cause of TTR amyloidoses. Nevertheless, an anti-amyloidogenic effect that prevents Aβ aggregation in vitro has recently been proposed for TTR. We have therefore explored the ability of three different types of TTR, human TTR (hTTR), mouse TTR (mTTR) and an engineered monomer of human TTR (M-TTR), to suppress the toxicity of HypF-N oligomers. Cell viability tests showed that hTTR, and to a greater extent M-TTR, can avoid the cell damage induced by protein oligomers, whereas mTTR does not show any protective effect. To shed light on the different behavior of the TTRs and on the molecular mechanism by which they can exert their potential protective ability, we have investigated the molecular structure of HypF-N oligomers after the incubation with TTRs. Thioflavin T assay and pyrene site-directed labeling showed that all the three types of TTR cannot structurally re-arrange toxic HypF-N oligomers into a nontoxic form. Intrinsic fluorescence measurements and SDS-PAGE indicated that TTRs are able to bind to the oligomers. Following this binding, hTTR, and to a greater extent M-TTR, induced the formation of larger species, as shown by AFM and turbidimetry measurements. By contrast, the interaction with mTTR does not induce such formation of clusters. These data indicate that TTR suppresses the toxicity of HypF-N oligomers similarly to well established chaperones with an efficacy that correlates with its ability to disassemble into monomers.
Finally, in Chapter 5, we tested the ability of HypF-N oligomers to induce the inflammatory response. In fact, increasing evidence suggests that neurodegeneration associated to aggregation of proteins is the result of many causes. The uncontrolled immune response in the brain has recently been established to play a central role in the onset and progression of diseases, such as Alzheimer’s disease and Parkinson’s disease. For this reason we explored the inflammatory response to the injury caused by HypF-N toxic and not toxic misfolded oligomers, with particular attention to the role of Hsps, Hsp70 and αB-crystallin, as immune signals and potential suppressors of HypF-N oligomer-mediated inflammation. The results, obtained by the evaluation of microglia activation in terms of cytokine-release, showed that both the toxic and the nontoxic oligomers triggered a pro-inflammatory response, as assessed through ELISA measurements of a set of cytokines. Interestingly, at concentrations in which the two types of oligomers share the ability of leaving unaltered the cellular viability evaluated by MTT tests, the nontoxic species were found to be stronger inducers of inflammation with respect to the toxic oligomers. Such immune property of the nontoxic aggregates could be linked to their lower level of internalization in microglia cells and to the consequent maintenance of their stimulus from outside the cells. In addition, the nontoxic oligomers and the assemblies of toxic oligomers neutralized by chaperones were found to have the ability to induce inflammation without affecting cellular viability.
In conclusion, the data presented in this thesis and collected entirely using misfolded protein oligomers by the model protein domain HypF-N have revealed (i) new structural determinants of protein oligomer toxicity, such as oligomer size and hydrophobic exposure and their interplay to determine toxicity, (ii) have revealed novel mechanisms by which molecular chaperones, including the emerging TTR, contribute to the maintenance of protein homeostasis and (iii) have shown how misfolded protein oligomers can be highly inflammatory, even in the absence of explicit toxicity.
Books on the topic "Protein deposition disease"
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Kuypers, Dirk R. J., and Morie A. Gertz. Light-chain deposition disease. Edited by Giuseppe Remuzzi. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0154_update_001.
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Light-chain deposition disease (LCDD) is characterized by extracellular tissue deposition of non-amyloid monoclonal immunoglobulin light chains (predominantly kappa light chains) in various organs including kidneys, heart, and liver. It is a rare cause of renal insufficiency. In two-thirds of cases it is associated with multiple myeloma, while in the remainder their monoclonal B cell proliferation does not meet the criteria for that diagnosis.Renal involvement occurs almost invariably and dominates the clinical course of the disease: greater than 90% of patients with LCDD have renal functional impairment; acute or rapidly progressive kidney failure usually develops over a period of months. Nephrotic-range proteinuria is present in 40–50% of patients while approximately 20% of patients develop nephrotic syndrome. Arterial hypertension and microscopic haematuria can be present. Extrarenal symptoms are related to affected organs with cardiomyopathy, cachexia, haemorrhages, infections, and MM progression as main causes of death.The diagnosis of LCDD is often delayed and whilst bone marrow examination will often identify associated MM, renal biopsy frequently provides the final diagnostic proof. Abnormal light chains can be detected and quantified by serum or urine protein electrophoresis and immunofixation. Quantification of urine and serum free kappa/lambda light chains has proven a useful screening tool and might also plays a role in therapeutic monitoring.Treatment consists of chemotherapy directed against the monoclonal immunoglobulin-producing plasma cells.
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Knight, Richard. Prion disease. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0319.
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Prion diseases (also known as transmissible spongiform encephalopathies (TSEs)) affect animals and humans, although only the human diseases will be discussed in this chapter. Despite TSEs having somewhat disparate causes and effects, there are unifying features: TSEs are brain diseases with neurodegenerative pathology, which is typically associated with spongiform change, and, most characteristically, there is tissue deposition of an abnormal structural form of the prion protein. Some of the TSEs are naturally acquired infections and, while others are not, they are potentially transmissible in certain circumstances.
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Lei, Peng, Scott Ayton, and Ashley I. Bush. Metal-Protein Attenuating Compounds in Neurodegenerative Diseases. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190233563.003.0015.
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Neurodegenerative disorders including Alzheimer’s (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are progressive diseases of the aging population with currently few therapeutic options. While aggregation and deposition of disease-specific proteins link the pathologies of these diseases, targeting these aggregating proteins with therapeutics has not yet been successful in clinical trial. This chapter profiles metals (copper, zinc, and iron) as alternative drug targets for neurodegeneration. Complex changes to metals occur in these neurodegenerative diseases. Accumulating evidences have demonstrated that perturbations to metal homeostasis contribute to the progression of neuronal dysfunction and death. Importantly, several phase II trials have shown that correcting metal dyshomeostasis improves clinical outcomes; the chapter argues that it is now time to explore the therapeutic utility of metal-based drugs in larger, phase III trials.
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Herrington, William G., Aron Chakera, and Christopher A. O’Callaghan. The kidney in systemic disease. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0170.
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Many systemic diseases can affect the kidney, including autoimmune conditions, malignancies, infections, and vascular diseases. Autoimmune conditions can cause inflammation of the glomeruli or tubules, or deposition of inflammatory proteins (AA amyloidosis). Malignancy can cause infiltration of normal renal tissue, immunoglobulin deposition in the renal vessels, glomeruli or tubules, or paraneoplastic renal dysfunction as occurs in secondary focal segmental glomerulosclerosis. Infections can cause inflammation in glomeruli, in association with immune complex deposition. Vascular disease and vasculitis reduce kidney blood supply and cause renal ischaemia. This chapter provides an overview of these diseases.
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Lachmann, Helen J., and Giampaolo Merlini. The patient with amyloidosis. Edited by Giuseppe Remuzzi. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0152.
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Amyloidosis is a disorder of protein folding in which normally soluble plasma proteins are deposited in the extracellular space in an abnormal insoluble fibrillar form. The process of amyloid formation and deposition causes cytotoxicity and progressive organ dysfunction. Amyloid is remarkably diverse and can be hereditary or acquired, localized or systemic, and lethal or merely an incidental finding. The most important numerically are AL amyloidosis, in which the fibrils are composed of monoclonal immunoglobulin light chains, and AA amyloidosis, in which the acute phase reactant Serum Amyloid A component forms the fibrils.The kidney is involved in 75% of patients with systemic amyloidosis. Heavy proteinuria or nephrotic syndrome is characteristic of most amyloid variants.Without treatment, systemic disease is usually fatal but measures that reduce the supply of amyloid fibril precursor proteins can result in regression of amyloid deposits, prevention of organ failure, and improved quality of life and survival. Early diagnosis, before irreversible organ damage has occurred, is the key to effective treatment. Recent advances in diagnosis and therapy have much improved the outlook of patients with AL amyloidosis, but agents with broader promise are under investigation.
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Mittal, Sajjan. Amyloidosis. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0181.
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Amyloidosis is a multisystem disease caused by the extracellular deposition of insoluble abnormal fibrils that injure tissues and organs. The fibrils are formed by the aggregation of misfolded, normally soluble proteins. Systemic amyloid light-chain (AL) amyloidosis (primary amyloidosis) is the commonest type of amyloidosis in the developed world, accounting for 80% of cases. The remainder are due to AA amyloidosis (secondary or reactive amyloidosis), familial amyloidosis, or other rare types of amyloidosis. The most common clinical features at diagnosis are nephrotic syndrome, heart failure (typically with predominant right heart failure), sensorimotor and/or autonomic peripheral neuropathy, and hepatosplenomegaly.
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Badimon, Lina, Felix C. Tanner, Giovanni G. Camici, and Gemma Vilahur. Pathophysiology of thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198755777.003.0018.
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Ischaemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are mainly a consequence of a sudden thrombotic occlusion of the vessel lumen. Arterial thrombosis usually develops on top of a disrupted atherosclerotic plaque because of the exposure of thrombogenic material, such as collagen fibrils and tissue factor (TF), to the flowing blood. TF, either expressed by subendothelial cells, macrophage- and/or vascular smooth muscle-derived foam-cells in atherosclerotic plaques, is a key element in the initiation of thrombosis due to its ability to induce thrombin formation (a potent platelet agonist) and subsequent fibrin deposition at sites of vascular injury. Adhered platelets at the site of injury also play a crucial role in the pathophysiology of atherothrombosis. Platelet surface receptors (mainly glycoproteins) interact with vascular structures and/or Von Willebrand factor triggering platelet activation signalling events, including an increase in intracellular free Ca2+, exposure of a pro-coagulant surface, and secretion of platelet granule content. On top of this, interaction between soluble agonists and platelet G-coupled protein receptors further amplifies the platelet activation response favouring integrin alpha(IIb)beta(3) activation, an essential step for platelet aggregation. Blood-borne TF and microparticles have also been shown to contribute to thrombus formation and propagation. As thrombus evolves different circulating cells (red-blood cells and leukocytes, along with occasional undifferentiated cells) get recruited in a timely dependent manner to the growing thrombus and further entrapped by the formation of a fibrin mesh.
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Covic, Adrian, Mugurel Apetrii, Luminita Voroneanu, and David J. Goldsmith. Vascular calcification. Edited by David J. Goldsmith. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0120_update_001.
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Vascular calcification (VC) is a common feature of patients with advanced CKD and it could be, at least in part, the cause of increased cardiovascular mortality in these patients. From a morphologic point of view, there are at least two types of pathologic calcium phosphate deposition in the arterial wall—namely, intima calcification (mostly associated with atherosclerotic plaques) and media calcification (associated with stiffening of the vasculature, resulting in significantly adverse cardiovascular outcomes). Although VC was viewed initially as a passive phenomenon, it appears to be a cell-mediated, dynamic, and actively regulated process that closely resembles the formation of normal bone tissue, as discovered recently. VC seems to be the result of the dysregulation of the equilibrium between promoters and inhibitors. The determinants are mostly represented by altered calcium and phosphorus metabolism, secondary hyperparathyroidism, vitamin D excess, high fibroblast growth factor 23, and high levels of indoxyl sulphate or leptin; meanwhile, the inhibitors are vitamin K, fetuin A, matrix G1a protein, osteoprotegerin, and pyrophosphate. A number of non-invasive imaging techniques are available to investigate cardiac and vascular calcification: plain X-rays, to identify macroscopic calcifications of the aorta and peripheral arteries; two-dimensional ultrasound for investigating the calcification of carotid arteries, femoral arteries, and aorta; echocardiography, for assessment of valvular calcification; and, of course, computed tomography technologies, which constitute the gold standard for quantification of coronary artery and aorta calcification. All these methods have a series of advantages and limitations. The treatment/ prevention of VC is currently mostly around calcium-mineral bone disease interventions, and unproven. There are interesting hypotheses around vitamin K, Magnesium, sodium thiosulphate and other potential agents.
Book chapters on the topic "Protein deposition disease"
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Masters, Colin L., and Konrad Beyreuther. "Amyloid ßA4 protein deposition in Alzheimer’s disease and Down’s Syndrome." In Molecular Mechanisms of Aging, 185–94. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-84224-5_14.
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Selkoe, Dennis J. "Amyloid ß-Protein Deposition as a Seminal Pathogenetic Event in Alzheimer’s Disease." In Amyloid and Amyloidosis 1990, 713–17. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-011-3284-8_175.
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Yadav, Divyansh, and Seema Nara. "Nanozymes for Neurodegenerative Diseases." In Proceedings of the Conference BioSangam 2022: Emerging Trends in Biotechnology (BIOSANGAM 2022), 77–95. Dordrecht: Atlantis Press International BV, 2022. http://dx.doi.org/10.2991/978-94-6463-020-6_9.
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AbstractNeurodegenerative diseases are incurable diseases that get worse as time passes. These diseases are very heterogeneous in nature but have common characteristics like abnormal deposition of protein, glycation, inflammation in particular areas of the brain, and progressive neuronal loss due to oxidative stress. Among these, oxidative stress alone causes a high level of degeneration of neurons. To reduce oxidative stress, natural antioxidants are used but they have some drawbacks like instability, high cost and low reusability. To overcome this, nanozymes are introduced and we have emphasized on major nanozymes whose antioxidant capability has been proven which are gold nanozymes, fullerene, nanoceria, and quantum dots. Gold nanoparticles and their conjugates with other molecules can mimic the enzymatic activity of superoxide dismutase and catalase which decrease the amount of hydrogen peroxide and superoxide radicals in cells. Gold Nanozyme treatment reduces the oxidative stress, nitrite, and sulfhydryl levels in the brain and also rectifies the superoxide dismutase, glutathione, and catalase activity levels. Fullerenols has shown superoxide dismutase activity which was 268 times more effective than mannitol and 37 times more effective than Vitamin E for lipid radicals. Nanoceria has the ability to mimic Superoxide Dismutase as well as catalase activity, can also detoxify peroxynitrite. Quantum dots (QDs) like Graphene Oxide QDs can scavenge the reactive oxygen species and also show indirect activity which alleviates the pathogenesis of the disease. Thus, a nanozyme can be used as an efficient nanomedicine if it is tailored to possess high catalytic activity while eliminating all complications.
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Chaudhary, Rishabh, Mujeeba Rehman, Vipul Agarwal, Arjun Singh Kaushik, and Vikas Mishra. "Protein Aggregation in Neurodegenerative Diseases." In Neurodegenerative Diseases - Multifactorial Degenerative Processes, Biomarkers and Therapeutic Approaches (First Edition), 26–58. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815040913122010005.
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Protein aggregation-related diseases primarily affect the central nervous system and are involved in the pathogenesis of multiple neurodegenerative diseases as well as several rare hereditary disorders that involve the deposition of protein aggregates in the brain. These diseases include Alzheimer's, Parkinson, Huntington's disease, Prion diseases, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, etc. The aggregates usually consist of fibers containing misfolded protein with a betasheet conformation. As a result, proteins’ secondary structures change from α-helix to β-sheet, leading to the accumulation of harmful misfolded protein aggregates in the CNS. The misfolding, subsequent aggregation and accumulation of proteins in neurodegenerative diseases lead to cellular dysfunction, loss of synaptic connections and brain damage. This chapter discusses some of the important neurodegenerative diseases resulting from protein misfolding and explains the pathological mechanisms behind brain damage.
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S. Harrison, Jonathan, Yossi Cohen, Irina Ioffe, and Shlomo Bulvik. "An Historical Overview of the Amyloidoses." In Amyloidosis History and Perspectives [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.97826.
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The amyloidoses are a heterogenous group of clinical disorders that share the common finding of the abnormal deposition of insoluble proteins into various organs, with the result that these proteinaceous deposits disrupt cellular function and impair the integrity of the organs involved. Most typically, the abnormal protein deposition is the consequence of abnormal three dimensional folding of the culprit protein. The abnormal folding of the protein, in turn, may be due to a germ line mutation, may be due to an acquired mutation, or may be due to a polymorphism or characteristic of a normal protein that leads to abnormal folding, precipitation, and deposition of the protein, particularly when that protein is expressed at unusually high levels for a prolonged period of time. The clinical manifestations of an amyloid disorder are the consequences of the array of organs involved, the extent of amyloid deposition, and co-morbid conditions present in the individual patient. The array of organs involved, and the extent of organ involvement, in turn, depend in large part on the specific protein that is responsible for the amyloid deposition, and the process driving that protein’s production. In this chapter, a chronological overview is intended to summarize the critical insights into the patho-biology of amyloid accumulation of various types. These insights have allowed an improved understanding over time of the of the major subgroups and disease entities of the amyloidoses, leading to some degree of improvement in diagnosis and treatment outcomes. Unfortunately, as of this writing, treatment outcomes still remain poor for a large fraction of patients, and there is need for improvement in all aspects of the evaluation and management of these diseases.
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Takashima, Akihiko. "Animal Models of Amyloid/PS-1 Pathology." In Animal Models for Neurodegenerative Disease, 15–38. The Royal Society of Chemistry, 2011. http://dx.doi.org/10.1039/bk9781849731843-00015.
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Senile plaques and neurofibrillary tangles (NFTs) are major pathological proteinaceous anomalies that occur in the brains of Alzheimer's disease (AD) patients. Motivated by the amyloid hypothesis, animal models exhibiting Aβ deposition have been produced by crossbreeding mice overexpressing human mutant amyloid precursor protein (hAPP) with mice overexpressing mutant PS-1, the latter of which accelerates Aβ deposition in the brain. Most mouse models exhibiting Aβ deposition show memory deficits associated with synaptic plasticity impairments and synapse loss. In this chapter, I introduce the most commonly used amyloid/PS-1 transgenic mouse models that exhibit Aβ deposition and discuss some limitations of using these animal models to understand the devastating condition of AD.
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Vicenty-Rivera, Sonia, and Ingrid Bonilla-Mercado. "Cardiac Amyloidosis." In New Insights on Cardiomyopathy [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.109522.
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Cardiac amyloidosis is a protein-folding disorder mostly caused by abnormal deposition of either transthyretin proteins or light chain (AL) proteins, into one or more organs, including the heart. The main cardiac manifestations are right ventricular heart failure and arrhythmias. Extracardiac symptoms usually precede cardiac symptoms and are evident several years before the development of symptomatic cardiac problems. The prognosis is poor without appropriate management. Non-invasive evaluation with multi-imaging modalities has allowed earlier diagnosis, particularly when used in combination with monoclonal gammopathy evaluation. Management will vary depending on the subtype of amyloidosis. It consists of supportive treatment of cardiac-related symptoms, pharmacological treatment that targets amyloid fibrils formation and deposition, thus attacking the underlying disease, and addressing the management of extracardiac symptoms to improve the patients’ quality of life.
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Cambronero, Francis, and Angela L. Jefferson. "Hemodynamics in Alzheimer’s Disease and Vascular Cognitive Impairment and Dementia." In Vascular Disease, Alzheimer's Disease, and Mild Cognitive Impairment, 302–30. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780190634230.003.0014.
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Hemodynamic impairment is a prominent feature in aging, vascular cognitive impairment and dementia, and Alzheimer’s disease, including patterned changes in cerebral blood flow (CBF) that can be detected prior to concomitant pathologies. These CBF abnormalities drive vascular dysfunction through a variety of biological pathways and ultimately contribute to cerebrovascular disease associated with cognitive impairment. Importantly, the co-existence of cerebrovascular disease and Alzheimer’s disease is exceedingly common and worsens the progression of clinical symptoms, likely through accelerating neurotoxic protein deposition and the loss of cerebrovascular integrity. Emerging evidence further suggests that the brain may be more susceptible to subclinical cardiovascular dysfunction in aging adults, particularly since the accumulation of cardiovascular risk factors over the lifespan creates a more vulnerable vascular system. Although age-associated CBF dysregulation has varied and complex origins, it undoubtedly serves a critical role in the early progression of neurodegenerative disease and may help explain the considerable overlap between the most common clinical dementias.
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Ironside, James W., Matthew P. Frosch, and Bernardino Ghetti. "Human Prion Diseases." In Escourolle and Poirier's Manual of Basic Neuropathology, 149–60. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199929054.003.0006.
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This chapter describes and illustrates the neuropathology of prion diseases, also known as transmissible spongiform encephalopathies. These diseases are characterized pathologically by varying combinations of spongiform change, neuronal loss, reactive gliosis, and prion protein (PrP) deposition. The morphologic pattern depends on the etiology of the disease and the genotype of the patient. Different clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (CJD) have been described depending on the PRNP codon 129 genotype and the PrP isotype. A novel form known as variably protease-sensitive prionopathy has been recently identified. Familial prion diseases include familial CJD, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Over 40 different PRNP mutations have been identified. Acquired prion diseases include Kuru; iatrogenic CJD, particularly in recipients of contaminated human pituitary hormone, and variant CJD, which seems closely related to bovine spongiform encephalopathy.
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Jiang, Kun, Yongqi Zhu, and Lei Zhang. "New Prospects for Stem Cell Therapy in Alzheimer’s Disease." In Hippocampus - Cytoarchitecture and Diseases. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.100334.
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Alzheimer’s disease (AD) is a kind of neurodegenerative disease with insidious onset and progressive progression. The etiology of AD may be related to the loss of neurons, astrocytes, and microglial in the nervous system. Exogenous stem cell transplantation has brought hope to the treatment of AD. Stem cell transplantation can reduce amyloid β-protein (Aβ) deposition and Tau phosphorylation, and provide secretory factor support to improve learning and memory deficits. The purpose of this review is to provide an overview of the relationship between different stem cell species and the treatment of AD, and also summarize current experimental stem cell therapy strategies and their potential clinical applications in the future.
Conference papers on the topic "Protein deposition disease"
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Abakumets, V. Y., and K. Ya Bulanava. "THE INFLUENCE OF INSULIN FIBRILLATION." In SAKHAROV READINGS 2021: ENVIRONMENTAL PROBLEMS OF THE XXI CENTURY. International Sakharov Environmental Institute of Belarusian State University, 2021. http://dx.doi.org/10.46646/sakh-2021-2-7-10.
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Violation of protein folding leads to the development of a number of systemic and neurodegenerative diseases-proteinopathy. In these pathologies, proteins acquire an incorrect conformation that differs from the native one, become functionally inactive, toxic, and prone to aggregation and deposition in various organs and tissues. There is a widespread hypothesis that the primary cytotoxic agents in the development of proteinopathies are protein oligomers that are prone to aggregation. These diseases include Parkinson’s disease, Creutzfeldt-Jakob disease, type 2 diabetes, and many others.
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Stork, Larissa Rosa, Lucca Stephani Ribeiro, Izabella Savergnini Deprá, Luísa D’Ávila Camargo, and Maria Angélica Santos Novaes. "Tau protein and its role in Alzheimer’s disease physiopathology: a literature review." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.132.
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Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a double proteinopathy: deposition of amyloid-β into plaques and hyperphosphorylation of Tau protein. Objectives: To understand the genetic and molecular aspects of Tau protein and its relationship with Alzheimer’s disease. Methods: We conducted a systematic literature search using Pubmed/ MEDLINE and ClinicalKey databases, applying the descriptors: “Alzheimer Disease” AND “Tau proteins’’ AND Tauopathies, during July and August of 2020. The inclusion criteria were English and Portuguese articles published between 2015 and 2020, with human limited study and free full text, excluding images, books, clinical tests, and narrative reviews. After analyzing titles and abstracts, we selected 12 articles and included 7 additional studies. Results: Mapt, the encoder gene of Tau, is located in the 17q21.3 locus and presents 16 exons that, when transcripted, originates 12 copies of mRNA by alternative splicing and 6 Tau’s isoforms. Tau is a microtubule-associated protein (MAP) responsible for cellular cytoskeleton stabilization and maintenance, promoting neuronal axonal transport. A kinase-phosphatase imbalance turns Tau hyperphosphorylated, disassociating it from tubulin and grouping it into insoluble paired helical filaments, which originates neurofibrillary tangles. The tauopathy’s progress causes neurotransmitter destabilization and neuronal death, inducing AD symptomatic manifestations. Conclusions: Due to the gradual worsening of the disease to more debilitating stages, studies focused on deepening the knowledge of genetic and molecular aspects of Tau protein are viable and promising alternatives to improve the quality of patient’s lives.
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Guelli, Mariana Sandoval Terra Campos, Daniela Bastos de Almeida Zampier, Lorena Araújo Silva Dias, and Marina de Oliveira Nunes Ibrahim. "Creutzfeldt-Jakob Disease - a literature review." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.126.
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Background: Creutzfeldt-Jakob disease (CJD) is a progressive, rare, fatal and rapid human neurodegenerative disease that occurs in the etiologies: sporadic (CJD), familial, iatrogenic (CJD) and CJD variant (CJV) in which cell prion protein (PrP) can be transmitted through animals. Objectives: Literature review about Creutzfeldt-Jakob diseaseDesign and setting: Literature review development in the Centro Universitário de Volta Redonda, Rio de Janeiro, Brazil. Methods: The Creutzfeldt-Jakob disease, infectious diseases and neuroinfection indexes were used in the PUBMED and Scielo databases. Results:CJD has different etiologies with different clinical and pathological phenotypes. CJDV shows psychiatric behaviors and symptoms followed by abnormalities, ataxia and dementia. The sporadic form is the most common, with a progressive clinical course with generalized brain deposition of abnormal prion protein aggregates (PrPTSE) that leads to spongiform change, gliosis and neuronal loss. CJD progresses to dementia and two or more symptoms: cerebellar or visual impairments; pyramidal or extrapyramidal signs; myoclonus; and akinetic mutism. Complex periods of acute wave in the electroencephalogram (EEG) are strongly suggestive of prionic diseases. Rapidly evolving field neuroimmune disorders have shown an increasing in autoantibody testing; attempt to diagnose a range of immune-mediated conditions. Evidence indicates that diffusion-weighted magnetic resonance imaging (DWI) is more sensitive for detecting signal abnormalities. Conclusion: The disease progresses to dementia, accompanied by myoclonus, pyramidal signs and characteristic EEG. It is a complex pathology, which has only symptomatic treatment and requires strict control of reservoirs and risk of contamination.
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Sewell-Loftin, M. K., and W. David Merryman. "The Role of SRC in Strain- and Ligand- Dependent Phenotypic Modulation of Mouse Embryonic Fibroblasts." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53604.
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Connective tissue fibrosis represents a significant portion of mortality and morbidity in our society. These diseases include many illnesses such as heart valve disease, atherosclerosis, macular degeneration, and cirrhosis, meaning that millions of lives are affected by these conditions each year. Fibrotic tissues form when quiescent fibroblasts activate becoming myofibroblasts, the phenotype of active tissue construction and fibrosis. During this process, the cells produce smooth muscle α-actin (αSMA), a contractile element considered to be the hallmark of cellular activation [1]. Following the production of αSMA, there is an increase in the synthesis of extracellular matrix (ECM) proteins, most notably type I collagen; this increase in ECM proteins causes the stiffening of the tissue characteristic of fibrotic disease. In non-disease states (such as wound healing or tissue development), the myofibroblasts will either deactivate, becoming fibroblasts again, or apoptose before tissue fibrosis occurs. However, when myofibroblasts persist, increased ECM protein deposition causes increased tissue stiffness and activates neighboring cells, causing the fibrosis to propagate. Currently there are no therapies to prevent or reverse fibrosis. Therefore a more thorough understanding of the dynamic mechanical environment and signaling pathways involved in the activation of fibroblasts is required to develop potential treatments.
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Tosatti, Jéssica, Adriana Fontes, Paulo Caramelli, and Karina Gomes. "EFFECTS OF RESVERATROL SUPPLEMENTATION ON THE COGNITIVE FUNCTION OF PATIENTS WITH ALZHEIMER’S DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS." In XIII Meeting of Researchers on Alzheimer's Disease and Related Disorders. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1980-5764.rpda026.
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Background: Alzheimer’s disease (AD) is characterized by a deposition of β-amyloid peptide and the neurofibrillary tangles of tau protein. Resveratrol is a neuroprotective agent, acting in the prevention of redox impairment, and could reduce neuronal damage in patients with AD. Objectives: Systematic review and meta-analysis about the effects of resveratrol supplementation on cognitive and functional performance in patients with AD. Methods: Databases were searched for primary studies that reported cognitive and functional performance based on ADAS-cog, ADCS-ADL or MMSE instruments in AD patients treated with resveratrol. Primary studies published up to May 2021 and without language and publication date restrictions were included. The measure of effect of the meta-analysis was presented as weighted mean difference (WMD). decrease in ADAS-cog scores [WMD: -3.69 points], and significant increases in ADCS-ADL [WMD: 5.65 points] and MMSE scores [WMD: 2.03 points] in the resveratrol intervention group, when compared to the placebo group. Conclusions: Resveratrol supplementation may result in improving cognitive and functional performance in AD patients.
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Lomakin, Aleksey, David B. Teplow, Daniel A. Kirschner, and George B. Benedek. "Nucleation and Growth of Amyloid β-Protein Fibrils: Detection of Nuclei and Quantitation of Rate Constants." In Photon Correlation and Scattering. Washington, D.C.: Optica Publishing Group, 1996. http://dx.doi.org/10.1364/pcs.1996.sab.3.
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Alzheimer's disease is a progressive, neurodegenerative disorder characterized by amyloid deposition in senile plaques in the cerebral parenchyma and vasculature.(1) These plaques are composed primarily of fibers of the amyloid β-protein, Aβ. A number of studies have provided information on the structure of fibrils formed both in vivo and in vitro, and on factors affecting fiber formation. Synthetic Aβ peptides also form fibers which are ultrastructurally indistinguishable from those isolated from the brain. These peptides have been utilized to examine how a variety of parameters, including temperature, pH, solvent composition, peptide concentration, and peptide sequence, influence the final structure of Aβ aggregates. What is substantially less understood, however, is the kinetics of Aβ fibril growth.
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Maia, Lucas Henrique, Thaís Galdino Diniz, Vitor Carvalho Caetano, Marina Gomes Diniz, Pedro Lucas Bessa dos Reis, Gabriela Vieira Marques da Costa Leão, Vitor Moreira Nunes, and Helton José dos Reis. "Antibiotic therapy as a risk factor in Parkinson’s disease." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.521.
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Background: Antibiotics exposure is related to gastrointestinal tract dysbiosis and appearance of systemic repercussions. Due to the correlation between Enteric Nervous System (ENS) and Central Nervous System (CNS), abnormalities in the gut microbiota have been associated with neurological disorders including Parkinson’s Disease (PD). Objectives: Search evidence in the scientific literature relating antibiotic therapy and Parkinson’s disease. Methods: A systematic review has been done using the descriptors “Parkinson’s disease”, “antibiotics” and “gut microbiota” in PubMed’s database. The research was conducted in april 2021, without temporal limitations, in english and portuguese. Results: Studies suggest that PD begins with intestinal inflammation and abnormal alpha-synuclein deposition in the ENS that follows, through nerves, to the CNS. Results show that leaky gut and dysbiosis preceded 5-10 years PD’s initial symptoms, while the intense exposure to antibiotics preceded 10-15 years the diagnostic. On average, PD patients received larger amounts of antibiotics than controls (p=0.021). Dysbiosis post-antibiotics presented reduced diversity of Bacteroidetes, Firmicutes and Prevotellaceae and growthing of Enterobacteriaceae, resulting in higher risk of gastrointestinal infections, higher rates of pro-inflammatory cytokines, increased permeability of gastrointestinal and brain-blood barriers and hyperexpression of the alpha-synuclein protein in the colon. Conclusion: Poorly controlled antibiotic therapy and its subsequent damage to gut microbiota anticipates PD’s early symptoms.
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Nakstad, Britt, and Torstein Lyberg. "LOCAL ACTIVATION OF COAGULATION AND FIBRINOLYSIS IN LUNG DISEASE IS REFLECTED IN BR0NCH0ALVE0LAR LAVAGE FLUID." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643054.
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Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of pulmonary inflammatory diseases.Ce11s of the monocyte/ macrophage lineage have a dualistic role in the balance between coagulation and fibrinolysis having the ability to synthesize both procoagulant factors and plasminogen activators. In the present studies bronchoa1veo1 ar lavage were performed on 128 patients with various lung diseases and 29 healthy controls.Both lung alveolar macrophages (LAM) and the supernatant bronchoalveolar lavage fluid (BALF) expressed two types of procoagulant activities a)thromboplastin and b) a direct factor X activator.The procoagulant in BALF was associated with membrane vesicles which sedimented at 100000g,lh.By electron microscopy the BALF ultrasediment was seen to consist for a large part of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. LAM from patients had significantly higher specific thromboplastin activity than LAM from controls (4,36 -0.98(SEM)vs.0.81± 0.14 U/mg cell protein).BALF collected from patients had significantly higher levels than BALF from controls of a ) thrombop1 astin(0.66-0.18vs.0.07 ±0.01 U/ml) b ) factor VII activity(1.33±0.31vs.0.48±0.06 U/ml) c)fibrin degradation products(presentin 28,7vs.0% of the cases) and d) fibronectin(491±103 vs.35±5 ng/ml ) In addition,the level of plasminogen activator was higher in controls than in patients(294±68 vs.!02±14 m U/m1).These studies show that activation products of the coagulation and fibrinolytic systems can be detected in BALF and that lung disease often is associated with abberations in the balance between these systems.Fibrin serves as a substrate for fibronectin and the increases in lavage fibronectin may reflect the development of lung fibrosis.
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Stern, David M., Sara Rimon, Todd Scott, and Peter P. Nawroth. "MODULATION OF ENDOTHELIAL CELL COAGULANT PROPERTIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642946.
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As the cells forming the luminal vascular surface, endothelium is strategically located to play a role in the regulation of coagulation. Participation of endothelium in coagulation involves specific receptors on the cell surface functioning at the level of initiation and propagation of hemostatic reactions. In the anticoagulant protein C pathway, for example, the receptor thrombomodulin initiates thrombin-mediated activation of protein C and a binding site for protein S on bovine endothelium promotes assembly of the functional activated protein C/protein S complex. Endothelium also synthesizes, stores and releases functional protein S constitutively and in response to specific stimuli such as norepinephrine.Since activation of protein C requires thrombin formation in proximity to the vessel wall, we have examined procoagulant reactions on the endothelial cell surface. Endothelium provides a receptor for Factor IX/IXa which is relatively selective for the enzyme form and facilitates Factor IXa-VIII-mediated activation of Factor X. Half-maximal Factor Xa formation occurs at a Factor IXa concentration of 0.4nM on endothelium, whereas lOnM is required on liposomes. This concentration of Factor IXa corresponds to that which results in half-maximal occupancy of endothelial cell Factor IXa binding sites in the presence of Factors VIII and X, thus correlating kinetics and binding measurements. Crosslinking and ligand blotting studies have shown that the receptor is a protein with a molecular weight of ∼160,000. The clinical significance of this receptor is suggested by the moderately severe bleeding disorder observed in a patient with hemophilia B due to an abnormal Factor IX molecule, Factor IXalabama (Factor IXala). Although the coagulant activity of Factor IXala is only mildly decreased on phospholipids, it is severely impaired on endothelium. The affinity of Factor IXala for the endothelial cell Factor X activation complex is decreased by 20-fold compared with the normal enzyme and the binding affinity is similarly decreased. Since the molecular defect in Factor IXala has been previously shown to consist of a single point mutation in the growth factor domain, this indicates a role for the growth factor domain in receptor, recognition.The picture of endothelial cell coagulant properties which emerges from these and other studies is one in which endothelium has either an anticoagulant or procoagulant potential, depending on modulation of receptor expression and release of secreted products. In the quiescent state, anticoagulant mechanisms predominate with only limited amounts of procoagulant activity: there is little tissue factor activity and only a basal level of receptors for Factor IX/lXa. Activation of endothelium by Tumor Necrosis Factor (TNF) or Interleukin 1 can shift this balance. Tissue factor synthesis and expression occurs in a dose-dependent manner, being half-maximal at a TNF concentration of about 150pM. TNF also increases the number of Factor IX/lXa binding sites. Concomitant with enhancement of endothelial cell procoagulant properties is a suppression of cell surface cofactor activity for the anticoagulant protein C pathway. Endothelial cell-dependent, thrombin-mediated activated protein C formation is decreased by 70-80% and activated protein C-protein S-mediated Factor Va inactivation decreases by over 90%. Following the in vivo infusion of Interleukin 1, similar changes in endothelial cell coagulant properties were observed on aortic segments with fibrin deposition occurring on the functionally altered, but morphologically intact endothelium. This modulation of endothelial cell coagulant properties could underlie the prothrombotic state associated with inflammatory disorders and could also explain the recently observed selective intravascular thrombosis of tumor vasculature seen in vivo in meth A sarcomas after administration of TNF.Thus, although endothelium was initially felt to be hemostatically inert, this apparent lack of activity actually masks a delicate balance of procoagulant and anticoagulant mechanisms. The balance can be effectively shifted by physiologic mediators, such as monokines, which alter receptor expression on the endothelial cell surface. Changes in endothelial cell hemostatic properties may be an early indicator of vessel wall disease and underlie the pathogenesis of localized thrombotic processes.
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Nakstad, Britt, and Torstein Lyberg. "PR0C0AGULANT ACTIVITIES IN HUMAN ALVEOLAR MACROPHAGES:." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643159.
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The coexistence of fibrin and tissue macrophages is a common finding in the histopathology of chronic inflammatory diseases of the lung.Fibrin deposition may occur as a result of activation of the extrinsic coagulation system,initiated by procoagulants generated by alveolar macrophages.In this study human alveolar macrophages (LAM) obtained by lavage of healthy donors were shown to express procoagulant factors,thromboplastin (tissue factor) and a direct factor X activator,probably a thromboplastin/ factor VII complex.In contrast to blood monocytes, LAM were only slightly susceptible for in vitro induction of thromboplastin activity (11,3 ± 2,6 (SEM)-fold and 1,3 t 0,2-fold activity increase after endotoxin stimulation).LAM were separated into four subpopulations by density gradient centrifugation.The specific thromboplastin activity of subpopulation cells varied inversely with their density (3,08 ± 0,42 U/mg cell protein for the least dense vs.0.49 ± 0.03 for the most dense subpopulation ).Low-density subpopulations of LAM released membrane material to the culture medium,which was sedimentable in the u1tracentrifuge and which expressed procoagulant activities with the same characteristics as the LAM procoagu1 ants.These findings suggest that alveolar macrophages and the membrane vesicles shed from their surface can contribute to local fibrin deposition in the lungs by expressing procoagulant factors.
Reports on the topic "Protein deposition disease"
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Sessa, Guido, and Gregory Martin. MAP kinase cascades activated by SlMAPKKKε and their involvement in tomato resistance to bacterial pathogens. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7699834.bard.
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The research problem: Pseudomonas syringae pv. tomato (Pst) and Xanthomonas campestrispv. vesicatoria (Xcv) are the causal agents of tomato bacterial speck and spot diseases, respectively. These pathogens colonize the aerial parts of the plant and cause economically important losses to tomato yield worldwide. Control of speck and spot diseases by cultural practices or chemicals is not effective and genetic sources of resistance are very limited. In previous research supported by BARD, by gene expression profiling we identified signaling components involved in resistance to Xcvstrains. Follow up experiments revealed that a tomato gene encoding a MAP kinase kinase kinase (MAPKKKe) is required for resistance to Xcvand Pststrains. Goals: Central goal of this research was to investigate the molecular mechanisms by which MAPKKKεand associated MAP kinase cascades regulate host resistance. Specific objectives were to: 1. Determine whether MAPKKKεplays a broad role in defense signaling in plants; 2. Identify components of MAP kinase cascades acting downstream of MAPKKKε; 3. Determine the role of phosphorylation-related events in the function of MAPKKKε; 4. Isolate proteins directly activated by MAPKKKε-associatedMAPK modules. Our main achievements during this research program are in the following major areas: 1. Characterization of MAPKKKεas a positive regulator of cell death and dissection of downstream MAP kinase cascades (Melech-Bonfil et al., 2010; Melech-Bonfil and Sessa, 2011). The MAPKKKεgene was found to be required for tomato resistance to Xcvand Pstbacterial strains and for hypersensitive response cell death triggered by different R gene/effector gene pairs. In addition, overexpression analysis demonstrated that MAPKKKεis a positive regulator of cell death, whose activity depends on an intact kinase catalytic domain. Epistatic experiments delineated a signaling cascade downstream of MAPKKKεand identified SIPKK as a negative regulator of MAPKKKε-mediated cell death. Finally, genes encoding MAP kinase components downstream of MAPKKKεwere shown to contribute to tomato resistance to Xcv. 2. Identification of tomato proteins that interact with MAPKKKεand play a role in plant immunity (Oh et al., 2011). We identified proteins that interact with MAPKKKε. Among them, the 14-3-3 protein TFT7 was required for cell death mediated by several R proteins. In addition, TFT7 interacted with the MAPKK SlMKK2 and formed homodimersin vivo. Thus, TFT7 is proposed to recruit SlMKK2 and MAPKKK client proteins for efficient signal transfer. 3. Development of a chemical genetic approach to identify substrates of MAPKKKε-activated MAP kinase cascades (Salomon et al., 2009, 2011). This approach is based on engineering the kinase of interest to accept unnatural ATP analogs. For its implementation to identify substrates of MAPKKKε-activated MAP kinase modules, we sensitized the tomato MAP kinase SlMPK3 to ATP analogs and verified its ability to use them as phosphodonors. By using the sensitized SlMPK3 and radiolabeled N6(benzyl)ATP it should be possible to tag direct substrates of this kinase. 4. Development of methods to study immunity triggered by pathogen-associated molecular patterns (PAMPs) in tomato and N. benthamiana plants (Kim et al., 2009; Nguyen et al. 2010). We developed protocols for measuring various PTI-associatedphenotypes, including bacterial populations after pretreatment of leaves with PAMPs, induction of reporter genes, callose deposition at the cell wall, activation of MAP kinases, and a luciferase-based reporter system for use in protoplasts. Scientific and agricultural significance: Our research activities discovered and characterized a signal transduction pathway mediating plant immunity to bacterial pathogens. Increased understanding of molecular mechanisms of immunity will allow them to be manipulated by both molecular breeding and genetic engineering to produce plants with enhanced natural defense against disease. In addition, we successfully developed new biochemical and molecular methods that can be implemented in the study of plant immunity and other aspects of plant biology.
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Kanner, Joseph, Edwin Frankel, Stella Harel, and Bruce German. Grapes, Wines and By-products as Potential Sources of Antioxidants. United States Department of Agriculture, January 1995. http://dx.doi.org/10.32747/1995.7568767.bard.
Full textAbstract:
Several grape varieties and red wines were found to contain large concentration of phenolic compounds which work as antioxidant in-vitro and in-vivo. Wastes from wine production contain antioxidants in large amounts, between 2-6% on dry material basis. Red wines but also white wines were found to prevent lipid peroxidation of turkey muscle tissues stored at 5oC. The antioxidant reaction of flavonoids found in red wines against lipid peroxidation were found to depend on the structure of the molecule. Red wine flavonoids containing an orthodihydroxy structure around the B ring were found highly active against LDL and membrane lipid peroxidation. The antioxidant activity of red wine polyphenols were also found to be dependent on the catalyzer used. In the presence of H2O2-activated myoglobin, the inhibition efficiency was malvidin 3-glucoside>catechin>malvidin>resveratol. However, in the presence of an iron redox cycle catalyzer, the order of effectiveness was resveratol>malvidin 3-glucoside = malvidin>catechin. Differences in protein binding were found to affect antioxidant activity in inhibiting LDL oxidation. A model protein such as BSA, was investigated on the antioxidant activity of phenolic compounds, grape extracts, and red wines in a lecithin-liposome model system. Ferulic acid followed by malvidin and rutin were the most efficient in inhibiting both lipid and protein oxidation. Catechin, a flavonal found in red-wines in relatively high concentration was found to inhibit myoglobin catalyzed linoleate membrane lipid peroxidation at a relatively very low concentration. This effect was studied by the determination of the by-products generated from linoleate during oxidation. The study showed that hydroperoxides are catalytically broken down, not to an alcohol but most probably to a non-radical adduct. The ability of wine-phenolics to reduce iron and from complexes with metals were also demonstrated. Low concentration of wine phenolics were found to inhibit lipoxygenase type II activity. An attempt to understand the bioavailability in humans of antocyanins from red wine showed that two antocyanins from red wine were found unchanged in human urine. Other antocyanins seems to undergo molecular modification. In hypercholesterolemic hamsters, aortic lipid deposition was significantly less in animals fed diets supplemented with either catechin or vitamin E. The rate of LDL accumulation in the carotid arteries was also significantly lower in the catechin and vitamin E animal groups. These results suggested a novel mechanism by which wine phenolics are associated with decreased risk of coronary heart diseases. This study proves in part our hypothesis that the "French Paradox" could be explained by the action of the antioxidant effects of phenolic compounds found at high concentration in red wines. The results of this study argue that it is in the interest of public health to increase the consumption of dietary plant falvonoids. Our results and these from others, show that the consumption of red wine or plant derived polyphenolics can change the antioxidant tone of animal and human plasma and its isolated components towards oxidative reactions. However, we need more research to better understand bioavailability and the mechanism of how polyphenolics affect health and disease.