A small molecule autophagy inducer exerts cytoprotection against α-synuclein toxicity.
Autophagosomes
/ drug effects
Autophagy
/ drug effects
Cytoprotection
/ drug effects
Drug Evaluation, Preclinical
Furans
/ pharmacology
HeLa Cells
Humans
Protein Aggregation, Pathological
/ drug therapy
Quinolines
/ pharmacology
Saccharomyces cerevisiae
Synucleinopathies
/ drug therapy
alpha-Synuclein
/ antagonists & inhibitors
AGK2
Autophagy
Neurodegeneration
Neuronal models
Protein misfolding diseases
Small molecule screen
Toxic protein aggregates
Yeast
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
05 Nov 2019
05 Nov 2019
Historique:
received:
19
05
2019
revised:
25
08
2019
accepted:
02
09
2019
pubmed:
7
9
2019
medline:
7
3
2020
entrez:
7
9
2019
Statut:
ppublish
Résumé
α-synucleopathies are protein-misfolding disorders occur primarily due to aggregation and toxicity of α-synuclein. This study characterized the small molecule AGK2 as a modifier of α-synuclein mediated toxicity in an autophagy dependent manner in both yeast and mammalian cell line models. In yeast system, AGK2 enhances autophagy to clear toxic α-synuclein aggregates in an autophagy dependent manner. Autophagy flux analyses revealed that AGK2 induces autophagy especially autolysosomes. Importantly, AGK2 induces autophagy in an mTOR independent manner. These features enable AGK2 to exert cytoprotective potential against α-synuclein mediated toxicity in different model systems.
Identifiants
pubmed: 31491404
pii: S0014-2999(19)30587-4
doi: 10.1016/j.ejphar.2019.172635
pii:
doi:
Substances chimiques
AGK2 compound
0
Furans
0
Quinolines
0
SNCA protein, human
0
alpha-Synuclein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
172635Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.