Alpha-Synuclein and the Endolysosomal System in Parkinson's Disease: Guilty by Association.
Parkinson’s disease
aggregation
alpha-synuclein
endolysosomal system
trafficking
vesicles
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
09 09 2021
09 09 2021
Historique:
received:
25
08
2021
revised:
06
09
2021
accepted:
06
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
14
1
2022
Statut:
epublish
Résumé
Abnormal accumulation of the protein α- synuclein (α-syn) into proteinaceous inclusions called Lewy bodies (LB) is the neuropathological hallmark of Parkinson's disease (PD) and related disorders. Interestingly, a growing body of evidence suggests that LB are also composed of other cellular components such as cellular membrane fragments and vesicular structures, suggesting that dysfunction of the endolysosomal system might also play a role in LB formation and neuronal degeneration. Yet the link between α-syn aggregation and the endolysosomal system disruption is not fully elucidated. In this review, we discuss the potential interaction between α-syn and the endolysosomal system and its impact on PD pathogenesis. We propose that the accumulation of monomeric and aggregated α-syn disrupt vesicles trafficking, docking, and recycling, leading to the impairment of the endolysosomal system, notably the autophagy-lysosomal degradation pathway. Reciprocally, PD-linked mutations in key endosomal/lysosomal machinery genes (LRRK2, GBA, ATP13A2) also contribute to increasing α-syn aggregation and LB formation. Altogether, these observations suggest a potential synergistic role of α-syn and the endolysosomal system in PD pathogenesis and represent a viable target for the development of disease-modifying treatment for PD and related disorders.
Identifiants
pubmed: 34572546
pii: biom11091333
doi: 10.3390/biom11091333
pmc: PMC8472725
pii:
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
Pays : Canada
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