Protein Quality Control Pathways at the Crossroad of Synucleinopathies

Eduardo P De Mattos, Anne Wentink, Carmen Nussbaum-Krammer, Christian Hansen, Steven Bergink, Ronald Melki, Harm H Kampinga*

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

5 Citaten (Scopus)
48 Downloads (Pure)

Samenvatting

The pathophysiology of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and many others converge at alpha-synuclein (α-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 α-Syn aggregation and toxicity. These encompass distinct cellular strategies that tightly balance protein production, stability, and degradation, ultimately regulating α-Syn levels. Here, we review the main aspects of α-Syn biology, focusing on the cellular PQC components that are at the heart of recognizing and disposing toxic, aggregate-prone α-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 α-Syn aggregates.

Originele taal-2English
Pagina's (van-tot)369-382
Aantal pagina's14
TijdschriftJournal of Parkinson's Disease
Volume10
Nummer van het tijdschrift2
Vroegere onlinedatum24-jan-2020
DOI's
StatusPublished - 3-apr-2020

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