Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: Examples of amyloidopathies, tauopathies and synucleinopathies
Progress in Neurobiology. 2017-08-01; 155: 171-193
DOI: 10.1016/j.pneurobio.2015.07.003
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Bourdenx M(1), Koulakiotis NS(2), Sanoudou D(3), Bezard E(1), Dehay B(4), Tsarbopoulos A(5).
Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(2)GAIA Research Center, Bioanalytical Department, The Goulandris Natural History
Museum, Kifissia 14562, Greece.
(3)National and Kapodistrian University of Athens Medical School, Department of
Internal Medicine, 75 Mikras Asias Street, Athens 11527, Greece.
(4)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France. Electronic address: .
(5)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: .
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.
Copyright © 2015 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.pneurobio.2015.07.003
PMID: 26209472 [Indexed for MEDLINE]