BL-918, a small-molecule activator of ULK1, induces cytoprotective autophagy for amyotrophic lateral sclerosis therapy

Autor: Wei Liu, Shi-ou Zhu, Yu-lin Guo, Long-fang Tu, Yong-qi Zhen, Rong-yan Zhao, Liang Ou-Yang, Hiroshi Kurihara, Rong-Rong He, Bo Liu
Rok vydání: 2022
Předmět:
Zdroj: Acta Pharmacologica Sinica. 44:524-537
ISSN: 1745-7254
1671-4083
DOI: 10.1038/s41401-022-00972-w
Popis: Amyotrophic lateral sclerosis (ALS) is one of the most common fatal neurodegenerative diseases in adults. ALS pathogenesis is associated with toxic SOD1 aggregates generated by mutant SOD1. Since autophagy is responsible for the clearance of toxic protein aggregates including SOD1 aggregates, autophagy induction has been considered as a potential strategy for treating ALS. Autophagic signaling is initiated by unc-51 like autophagy activating kinase 1 (ULK1) complex. We previously identified that BL-918 as a specific ULK1 activator, which exerted cytoprotective effect against Parkinson's disease in vitro and in vivo. In this study we investigated whether BL-918 exerted a therapeutic effect against ALS, and characterized its pharmacokinetic profile in rats. In hSOD
Databáze: OpenAIRE
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