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Journal Articles Journal of Parkinson's disease Year : 2020

Protein Quality Control Pathways at the Crossroad of Synucleinopathies

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Abstract

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.
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Dates and versions

cea-02458907 , version 1 (29-01-2020)

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Eduardo P. de Mattos, Anne Wentink, Carmen Nussbaum-Krammer, Christian Hansen, Steven Bergink, et al.. Protein Quality Control Pathways at the Crossroad of Synucleinopathies. Journal of Parkinson's disease, In press, 14 pp. ⟨10.3233/JPD-191790⟩. ⟨cea-02458907⟩
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