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Protein Quality Control Pathways at the Crossroad of Synucleinopathies
- Source :
- Journal of Parkinson's Disease. 10(2):369-382
- Publication Year :
- 2020
- Publisher :
- IOS Press, 2020.
-
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.
- Subjects :
- protein homeostasis
MULTIPLE SYSTEM ATROPHY
autophagy
IMPAIRS MACROAUTOPHAGY
LYSOSOMAL DEGRADATION
molecular chaperones
synucleinopathies
GLIAL CYTOPLASMIC INCLUSIONS
FIBRIL FORMATION
protein aggregation
Alpha-synuclein
PARKINSONS-DISEASE
MOLECULAR CHAPERONES
HEAT-SHOCK PROTEINS
MUTANT ALPHA-SYNUCLEIN
CHAPERONE-MEDIATED AUTOPHAGY
ubiquitin-proteasome system
Subjects
Details
- Language :
- English
- ISSN :
- 1877718X and 18777171
- Volume :
- 10
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Parkinson's Disease
- Accession number :
- edsair.dris...01423..e66fb4b3ee4cc5bd50863fd21353b41d