Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins.
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
21 Sep 2021
21 Sep 2021
Historique:
received:
04
03
2021
accepted:
23
07
2021
entrez:
22
9
2021
pubmed:
23
9
2021
medline:
23
9
2021
Statut:
epublish
Résumé
14-3-3s represent a family of highly conserved 30 kDa acidic proteins. 14-3-3s recognize and bind specific phospho-sequences on client partners and operate as molecular hubs to regulate their activity, localization, folding, degradation, and protein-protein interactions. 14-3-3s are also associated with the pathogenesis of several diseases, among which Parkinson's disease (PD). 14-3-3s are found within Lewy bodies (LBs) in PD patients, and their neuroprotective effects have been demonstrated in several animal models of PD. Notably, 14-3-3s interact with some of the major proteins known to be involved in the pathogenesis of PD. Here we first provide a detailed overview of the molecular composition and structural features of 14-3-3s, laying significant emphasis on their peculiar target-binding mechanisms. We then briefly describe the implication of 14-3-3s in the central nervous system and focus on their interaction with LRRK2, α-Synuclein, and Parkin, three of the major players in PD onset and progression. We finally discuss how different types of small molecules may interfere with 14-3-3s interactome, thus representing a valid strategy in the future of drug discovery.
Identifiants
pubmed: 34548498
doi: 10.1038/s41531-021-00230-6
pii: 10.1038/s41531-021-00230-6
pmc: PMC8455551
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
85Subventions
Organisme : NINDS NIH HHS
ID : P50 NS108675
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS112203
Pays : United States
Organisme : Ministry of Health, Italy | Agenzia Italiana del Farmaco, Ministero della Salute (Italian Medicines Agency)
ID : GR-2016-02363461
Organisme : NINDS NIH HHS
ID : R56 NS115767
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R56NS115767
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R01NS112203
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : P50NS108675
Informations de copyright
© 2021. The Author(s).
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