Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
received:
19
10
2022
accepted:
09
02
2023
revised:
18
01
2023
entrez:
1
3
2023
pubmed:
2
3
2023
medline:
4
3
2023
Statut:
epublish
Résumé
Although the discovery of the critical role of α-synuclein (α-syn) in the pathogenesis of Parkinson's disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, α-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of α-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting α-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.
Identifiants
pubmed: 36859484
doi: 10.1038/s41419-023-05672-9
pii: 10.1038/s41419-023-05672-9
pmc: PMC9977911
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
176Informations de copyright
© 2023. The Author(s).
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