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Updated: Dec 30, 2025

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
Protein Quality Control Pathways at the Crossroad of Synucleinopathies
Eduardo P De Mattos1, Anne Wentink2, Carmen Nussbaum-Krammer2
1Department of Biomedical Sciences of Cells & Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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.
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