BL-918 activates PINK1/Parkin signaling pathway to ameliorate the progression of Parkinson's disease

被引:0
|
作者
Wang, Yi [1 ,2 ]
Luo, Siyuan [1 ]
Su, Huili [1 ,2 ]
Wang, Zhimeng [1 ,2 ]
Chu, Ling [1 ]
Zhang, Conggang [1 ,2 ]
机构
[1] Tsinghua Univ, Sch Pharmaceut Sci, Beijing, Peoples R China
[2] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
ATP SYNTHASE; PINK1; UBIQUITIN; MITOCHONDRIA; SORAFENIB; MUTATIONS;
D O I
10.1016/j.jbc.2024.107543
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The pathogenesis of Parkinson's disease (PD) has been associated with mitochondrial dysfunction. Given that the PINK1/Parkin pathway governs mitochondrial quality control by inducing mitophagy to remove damaged mitochondria, therapeutic approaches to activate PINK1/Parkin-mediated mitophagy have the potential in the treatment of PD. Here, we have identified a new small molecule, BL-918, as an inducer of mitophagy via activating the PINK1/Parkin pathway. BL-918 triggers PINK1 accumulation and Parkin mitochondrial translocation to initiate PINK1/Parkin-mediated mitophagy. We found that mitochondrial membrane potential and mitochondrial permeability transition pore were involved in BL918-induced PINK1/Parkin pathway activation. Moreover, we showed that BL-918 mitigated PD progression in MPTPinduced PD mice in a PINK1-dependent manner. Our results unravel a new activator of the PINK1/Parkin signaling pathway and provide a potential strategy for the treatment of PD and other diseases with dysfunctional mitochondria.
引用
收藏
页数:12
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