Protein Quality Control Pathways at the Crossroad of Synucleinopathies
(2020) In Journal of Parkinson's Disease 10(2). p.369-382- 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... (More)
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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- author
- De Mattos, Eduardo P. ; Wentink, Anne ; Nussbaum-Krammer, Carmen ; Hansen, Christian LU ; Bergink, Steven ; Melki, Ronald and Kampinga, Harm H.
- organization
- publishing date
- 2020-04-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alpha-synuclein, autophagy, molecular chaperones, protein aggregation, protein homeostasis, synucleinopathies, ubiquitin-proteasome system
- in
- Journal of Parkinson's Disease
- volume
- 10
- issue
- 2
- pages
- 14 pages
- publisher
- IOS Press
- external identifiers
-
- pmid:31985474
- scopus:85083041835
- ISSN
- 1877-7171
- DOI
- 10.3233/JPD-191790
- language
- English
- LU publication?
- yes
- id
- 3c20e31f-0eb9-48b0-84f3-97a2fd30c2e8
- date added to LUP
- 2020-05-11 15:43:13
- date last changed
- 2024-09-04 21:43:45
@article{3c20e31f-0eb9-48b0-84f3-97a2fd30c2e8, abstract = {{<p>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.</p>}}, author = {{De Mattos, Eduardo P. and Wentink, Anne and Nussbaum-Krammer, Carmen and Hansen, Christian and Bergink, Steven and Melki, Ronald and Kampinga, Harm H.}}, issn = {{1877-7171}}, keywords = {{Alpha-synuclein; autophagy; molecular chaperones; protein aggregation; protein homeostasis; synucleinopathies; ubiquitin-proteasome system}}, language = {{eng}}, month = {{04}}, number = {{2}}, pages = {{369--382}}, publisher = {{IOS Press}}, series = {{Journal of Parkinson's Disease}}, title = {{Protein Quality Control Pathways at the Crossroad of Synucleinopathies}}, url = {{http://dx.doi.org/10.3233/JPD-191790}}, doi = {{10.3233/JPD-191790}}, volume = {{10}}, year = {{2020}}, }