α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies
Synucleinopathies are neurodegenerative disorders characterized by the accumulation of α-synuclein containing Lewy bodies. Ubiquitination, a key post-translational modification, has been recognized as a pivotal regulator of α-synuclein’s cellular dynamics, influencing its degradation, aggregation, a...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-11-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1498459/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850194377885876224 |
|---|---|
| author | Hung-Hsiang Ho Hung-Hsiang Ho Simon S. Wing Simon S. Wing |
| author_facet | Hung-Hsiang Ho Hung-Hsiang Ho Simon S. Wing Simon S. Wing |
| author_sort | Hung-Hsiang Ho |
| collection | DOAJ |
| description | Synucleinopathies are neurodegenerative disorders characterized by the accumulation of α-synuclein containing Lewy bodies. Ubiquitination, a key post-translational modification, has been recognized as a pivotal regulator of α-synuclein’s cellular dynamics, influencing its degradation, aggregation, and associated neurotoxicity. This review examines comprehensively the current understanding of α-synuclein ubiquitination and its role in the pathogenesis of synucleinopathies, particularly in the context of Parkinson’s disease. We explore the molecular mechanisms responsible for α-synuclein ubiquitination, with a focus on the roles of E3 ligases and deubiquitinases implicated in the degradation process which occurs primarily through the endosomal lysosomal pathway. The review further discusses how the dysregulation of these mechanisms contributes to α-synuclein aggregation and LB formation and offers suggestions for future investigations into the role of α-synuclein ubiquitination. Understanding these processes may shed light on potential therapeutic avenues that can modulate α-synuclein ubiquitination to alleviate its pathological impact in synucleinopathies. |
| format | Article |
| id | doaj-art-af4bd9c715fb44778d19f2a9fdc58b23 |
| institution | OA Journals |
| issn | 1662-5099 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj-art-af4bd9c715fb44778d19f2a9fdc58b232025-08-20T02:14:01ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-11-011710.3389/fnmol.2024.14984591498459α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodiesHung-Hsiang Ho0Hung-Hsiang Ho1Simon S. Wing2Simon S. Wing3Department of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, QC, CanadaIntegrated Program in Neuroscience, McGill University, Montreal, QC, CanadaDepartment of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, QC, CanadaIntegrated Program in Neuroscience, McGill University, Montreal, QC, CanadaSynucleinopathies are neurodegenerative disorders characterized by the accumulation of α-synuclein containing Lewy bodies. Ubiquitination, a key post-translational modification, has been recognized as a pivotal regulator of α-synuclein’s cellular dynamics, influencing its degradation, aggregation, and associated neurotoxicity. This review examines comprehensively the current understanding of α-synuclein ubiquitination and its role in the pathogenesis of synucleinopathies, particularly in the context of Parkinson’s disease. We explore the molecular mechanisms responsible for α-synuclein ubiquitination, with a focus on the roles of E3 ligases and deubiquitinases implicated in the degradation process which occurs primarily through the endosomal lysosomal pathway. The review further discusses how the dysregulation of these mechanisms contributes to α-synuclein aggregation and LB formation and offers suggestions for future investigations into the role of α-synuclein ubiquitination. Understanding these processes may shed light on potential therapeutic avenues that can modulate α-synuclein ubiquitination to alleviate its pathological impact in synucleinopathies.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1498459/fullα-synucleinLewy bodyubiquitinParkinson’s diseaseendosomelysosome |
| spellingShingle | Hung-Hsiang Ho Hung-Hsiang Ho Simon S. Wing Simon S. Wing α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies Frontiers in Molecular Neuroscience α-synuclein Lewy body ubiquitin Parkinson’s disease endosome lysosome |
| title | α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies |
| title_full | α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies |
| title_fullStr | α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies |
| title_full_unstemmed | α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies |
| title_short | α-Synuclein ubiquitination – functions in proteostasis and development of Lewy bodies |
| title_sort | α synuclein ubiquitination functions in proteostasis and development of lewy bodies |
| topic | α-synuclein Lewy body ubiquitin Parkinson’s disease endosome lysosome |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1498459/full |
| work_keys_str_mv | AT hunghsiangho asynucleinubiquitinationfunctionsinproteostasisanddevelopmentoflewybodies AT hunghsiangho asynucleinubiquitinationfunctionsinproteostasisanddevelopmentoflewybodies AT simonswing asynucleinubiquitinationfunctionsinproteostasisanddevelopmentoflewybodies AT simonswing asynucleinubiquitinationfunctionsinproteostasisanddevelopmentoflewybodies |