Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins

Abstract 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 as...

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Autores principales:	E. Giusto, T. A. Yacoubian, E. Greggio, L. Civiero
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/57a55e33f86545c39431beb496763fde
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spelling	oai:doaj.org-article:57a55e33f86545c39431beb496763fde2021-12-02T18:14:00ZPathways to Parkinson’s disease: a spotlight on 14-3-3 proteins10.1038/s41531-021-00230-62373-8057https://doaj.org/article/57a55e33f86545c39431beb496763fde2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00230-6https://doaj.org/toc/2373-8057Abstract 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.E. GiustoT. A. YacoubianE. GreggioL. CivieroNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 E. Giusto T. A. Yacoubian E. Greggio L. Civiero Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
description	Abstract 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.
format	article
author	E. Giusto T. A. Yacoubian E. Greggio L. Civiero
author_facet	E. Giusto T. A. Yacoubian E. Greggio L. Civiero
author_sort	E. Giusto
title	Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
title_short	Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
title_full	Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
title_fullStr	Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
title_full_unstemmed	Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
title_sort	pathways to parkinson’s disease: a spotlight on 14-3-3 proteins
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/57a55e33f86545c39431beb496763fde
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Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins

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