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Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: Examples of amyloidopathies, tauopathies and synucleinopathies.
Prog Neurobiol. 2017 Aug; 155:171-193.PN

Abstract

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative diseases that generate important health-related direct and indirect socio-economic costs. They are characterized by severe neuronal losses in several disease-specific brain regions associated with deposits of aggregated proteins. In Alzheimer's disease, β-amyloid peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein tau are the two main neuropathological lesions, while Parkinson's disease is defined by the presence of Lewy Bodies that are intraneuronal proteinaceous cytoplasmic inclusions. α-Synuclein has been identified as a major protein component of Lewy Bodies and heavily implicated in the pathogenesis of Parkinson's disease. In the past few years, evidence has emerged to explain how these aggregate-prone proteins can undergo spontaneous self-aggregation, propagate from cell to cell, and mediate neurotoxicity. Current research now indicates that oligomeric forms are probably the toxic species. This article discusses recent progress in the understanding of the pathogenesis of these diseases, with a focus on the underlying mechanisms of protein aggregation, and emphasizes the pathophysiological molecular mechanisms leading to cellular toxicity. Finally, we present the putative direct link between β-amyloid peptide and tau in causing toxicity in Alzheimer's disease as well as α-synuclein in Parkinson's disease, along with some of the most promising therapeutic strategies currently in development for those incurable neurodegenerative disorders.

Authors+Show Affiliations

Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.GAIA Research Center, Bioanalytical Department, The Goulandris Natural History Museum, Kifissia 14562, Greece.National and Kapodistrian University of Athens Medical School, Department of Internal Medicine, 75 Mikras Asias Street, Athens 11527, Greece.Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. Electronic address: benjamin.dehay@u-bordeaux.fr.GAIA Research Center, Bioanalytical Department, The Goulandris Natural History Museum, Kifissia 14562, Greece; National and Kapodistrian University of Athens Medical School, Department of Pharmacology, 75 Mikras Asias Street, Athens 11527, Greece. Electronic address: atsarbop@med.uoa.gr.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

26209472

Citation

Bourdenx, Mathieu, et al. "Protein Aggregation and Neurodegeneration in Prototypical Neurodegenerative Diseases: Examples of Amyloidopathies, Tauopathies and Synucleinopathies." Progress in Neurobiology, vol. 155, 2017, pp. 171-193.
Bourdenx M, Koulakiotis NS, Sanoudou D, et al. Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: Examples of amyloidopathies, tauopathies and synucleinopathies. Prog Neurobiol. 2017;155:171-193.
Bourdenx, M., Koulakiotis, N. S., Sanoudou, D., Bezard, E., Dehay, B., & Tsarbopoulos, A. (2017). Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: Examples of amyloidopathies, tauopathies and synucleinopathies. Progress in Neurobiology, 155, 171-193. https://doi.org/10.1016/j.pneurobio.2015.07.003
Bourdenx M, et al. Protein Aggregation and Neurodegeneration in Prototypical Neurodegenerative Diseases: Examples of Amyloidopathies, Tauopathies and Synucleinopathies. Prog Neurobiol. 2017;155:171-193. PubMed PMID: 26209472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: Examples of amyloidopathies, tauopathies and synucleinopathies. AU - Bourdenx,Mathieu, AU - Koulakiotis,Nikolaos Stavros, AU - Sanoudou,Despina, AU - Bezard,Erwan, AU - Dehay,Benjamin, AU - Tsarbopoulos,Anthony, Y1 - 2015/07/21/ PY - 2015/02/06/received PY - 2015/06/01/revised PY - 2015/07/17/accepted PY - 2015/7/26/pubmed PY - 2018/4/12/medline PY - 2015/7/26/entrez KW - Alzheimer's disease KW - Neurodegeneration KW - Parkinson's disease KW - Protein aggregation KW - Spreading KW - Therapeutic SP - 171 EP - 193 JF - Progress in neurobiology JO - Prog. Neurobiol. VL - 155 N2 - Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative diseases that generate important health-related direct and indirect socio-economic costs. They are characterized by severe neuronal losses in several disease-specific brain regions associated with deposits of aggregated proteins. In Alzheimer's disease, β-amyloid peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein tau are the two main neuropathological lesions, while Parkinson's disease is defined by the presence of Lewy Bodies that are intraneuronal proteinaceous cytoplasmic inclusions. α-Synuclein has been identified as a major protein component of Lewy Bodies and heavily implicated in the pathogenesis of Parkinson's disease. In the past few years, evidence has emerged to explain how these aggregate-prone proteins can undergo spontaneous self-aggregation, propagate from cell to cell, and mediate neurotoxicity. Current research now indicates that oligomeric forms are probably the toxic species. This article discusses recent progress in the understanding of the pathogenesis of these diseases, with a focus on the underlying mechanisms of protein aggregation, and emphasizes the pathophysiological molecular mechanisms leading to cellular toxicity. Finally, we present the putative direct link between β-amyloid peptide and tau in causing toxicity in Alzheimer's disease as well as α-synuclein in Parkinson's disease, along with some of the most promising therapeutic strategies currently in development for those incurable neurodegenerative disorders. SN - 1873-5118 UR - https://www.unboundmedicine.com/medline/citation/26209472/Protein_aggregation_and_neurodegeneration_in_prototypical_neurodegenerative_diseases:_Examples_of_amyloidopathies_tauopathies_and_synucleinopathies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-0082(15)00077-5 DB - PRIME DP - Unbound Medicine ER -