Protein quality control pathways at the crossroad of synucleinopathies

Bidragets oversatte titel: protein kvalitets kontrolveje ved skilleveje for synukleinopatier

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

Publikation: Bidrag til tidsskriftReviewpeer review

Abstract

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.
Bidragets oversatte titelprotein kvalitets kontrolveje ved skilleveje for synukleinopatier
OriginalsprogEngelsk
TidsskriftJournal of Parkinson's Disease
Vol/bind10
Udgave nummer2
Sider (fra-til)369-382
Antal sider14
DOI
StatusUdgivet - 24 jan. 2020
Udgivet eksterntJa

Emneord

  • Sygdom, sundhedsvidenskab og sygepleje

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