Molecular chaperones and associated cellular clearance mechanisms against toxic protein conformers in Parkinson's disease.

Détails

ID Serval
serval:BIB_5A804540D94D
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Molecular chaperones and associated cellular clearance mechanisms against toxic protein conformers in Parkinson's disease.
Périodique
Neuro-degenerative Diseases
Auteur(s)
Hinault M.P., Farina-Henriquez-Cuendet A., Goloubinoff P.
ISSN
1660-2862 (Electronic)
ISSN-L
1660-2854
Statut éditorial
Publié
Date de publication
2011
Volume
8
Numéro
6
Pages
397-412
Langue
anglais
Résumé
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder marked by the loss of dopaminergic neurons (in particular in the substantia nigra) causing severe impairment of movement coordination and locomotion, associated with the accumulation of aggregated α-synuclein (α-Syn) into proteinaceous inclusions named Lewy bodies. Various early forms of misfolded α-Syn oligomers are cytotoxic. Their formation is favored by mutations and external factors, such as heavy metals, pesticides, trauma-related oxidative stress and heat shock. Here, we discuss the role of several complementing cellular defense mechanisms that may counteract PD pathogenesis, especially in youth, and whose effectiveness decreases with age. Particular emphasis is given to the 'holdase' and 'unfoldase' molecular chaperones that provide cells with potent means to neutralize and scavenge toxic protein conformers. Because chaperones can specifically recognize misfolded proteins, they are key specificity factors for other cellular defenses, such as proteolysis by the proteasome and autophagy. The efficiency of the cellular defenses decreases in stressed or aging neurons, leading to neuroinflammation, apoptosis and tissue loss. Thus, drugs that can upregulate the molecular chaperones, the ubiquitin-proteasome system and autophagy in brain tissues are promising avenues for therapies against PD and other mutation-, stress- or age-dependent protein-misfolding diseases.
Mots-clé
Animals, Antiparkinson Agents/therapeutic use, Autophagy, Cells/metabolism, Humans, Molecular Chaperones/metabolism, Molecular Chaperones/physiology, Parkinson Disease/drug therapy, Parkinson Disease/genetics, Peptide Hydrolases/metabolism, alpha-Synuclein/metabolism
Pubmed
Web of science
Création de la notice
18/05/2011 10:36
Dernière modification de la notice
20/08/2019 15:13
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