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Protein quality control pathways at the crossroad of synucleinopathies

The pathophysiology of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and many others converge at alpha-synuclein (alpha-Syn) aggregation. Although it is still not entirely clear what precise biophysical processes act as triggers, cumulative evidence points towards a c...

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Main Authors: Mattos, Eduardo P. de (Author) , Wentink, Anne (Author) , Nussbaum-Krammer, Carmen (Author) , Hansen, Christian (Author) , Bergink, Steven (Author) , Melki, Ronald (Author) , Kampinga, Harm H. (Author)
Format: Article (Journal)
Language:English
Published: 2 January 2020
In: Journal of Parkinson's Disease
Year: 2020, Volume: 10, Issue: 2, Pages: 369-382
ISSN:1877-718X
DOI:10.3233/JPD-191790
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3233/JPD-191790
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Author Notes:Eduardo P. De Mattos, Anne Wentink, Carmen Nussbaum-Krammer, Christian Hansen, Steven Bergink, Ronald Melki, Harm H. Kampinga
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Summary:The pathophysiology of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and many others converge at alpha-synuclein (alpha-Syn) aggregation. Although it is still not entirely clear what precise biophysical processes act as triggers, cumulative evidence points towards a crucial role for protein quality control (PQC) systems in modulating alpha-Syn aggregation and toxicity. These encompass distinct cellular strategies that tightly balance protein production, stability, and degradation, ultimately regulating alpha-Syn levels. Here, we review the main aspects of alpha-Syn biology, focusing on the cellular PQC components that are at the heart of recognizing and disposing toxic, aggregate-prone alpha-Syn assemblies: molecular chaperones and the ubiquitin-proteasome system and autophagy-lysosome pathway, respectively. A deeper understanding of these basic protein homeostasis mechanisms might contribute to the development of new therapeutic strategies envisioning the prevention and/or enhanced degradation of alpha-Syn aggregates.
Item Description:Gesehen am 02.07.2020
Physical Description:Online Resource
ISSN:1877-718X
DOI:10.3233/JPD-191790

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