Author:
Zhang Qian,Hu Changpeng,Huang Jingbin,Liu Wuyi,Lai Wenjing,Leng Faning,Tang Qin,Liu Yali,Wang Qing,Zhou Min,Sheng Fangfang,Li Guobing,Zhang Rong
Abstract
Abstract
Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of the midbrain and the striatum and is an important pathologic basis of Parkinson’s disease (PD). Recent research has shown that dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergic nerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study showed that Drp1 knockdown inhibited aberrant mitochondrial fission and apoptosis. Importantly, we found that ROCK1 was activated in an MPP+-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632 blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cells by suppressing Drp1 dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms in a PD mouse model by inhibiting Drp1-mediated aberrant mitochondrial fission and apoptosis. Collectively, our findings suggest an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cell apoptosis via the activation of Drp1-induced aberrant mitochondrial fission.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Chongqing
Clinical Research Projects of second Affiliated Hospital, Army Medical University
Publisher
Springer Science and Business Media LLC
Subject
Clinical Biochemistry,Molecular Biology,Molecular Medicine,Biochemistry
Cited by
50 articles.
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