粒体自噬
帕金
神经保护
线粒体
细胞生物学
生物
神经科学
品脱1
LRRK2
自噬
帕金森病
生物化学
疾病
细胞凋亡
医学
基因
突变
内科学
作者
Shalini Mani,Divya Jindal,Hitesh Chopra,Saurabh Kumar Jha,Sachin Kumar Singh,Gulam Md. Ashraf,Mehnaz Kamal,Danish Iqbal,Dinesh Kumar Chellappan,Abhijit Dey,Saikat Dewanjee,Keshav K. Singh,Shreesh Ojha,Inderbir Singh,Rupesh K. Gautam,Niraj Kumar Jha
标识
DOI:10.1016/j.neubiorev.2022.104871
摘要
Neurons depend on mitochondrial functions for membrane excitability, neurotransmission, and plasticity. Mitochondrial dynamics are important for neural cell maintenance. To maintain mitochondrial homeostasis, lysosomes remove dysfunctional mitochondria through mitophagy. Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria. In many neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), mitophagy is disrupted in neurons. Mitophagy is regulated by several proteins; recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been suggested to negatively regulate the Parkin-dependent mitophagy pathway. Thus, ROCK2 inhibition may be a promising therapy for NDDs. This review summarizes the mitophagy pathway, the role of ROCK2 in Parkin-dependent mitophagy regulation, and mitophagy impairment in the pathology of AD. We further discuss different ROCK inhibitors (synthetic drugs, natural compounds, and gene therapy-based approaches) and examine their effects on triggering neuronal growth and neuroprotection in AD and other NDDs. This comprehensive overview of the role of ROCK in mitophagy inhibition provides a possible explanation for the significance of ROCK inhibitors in the therapeutic management of AD and other NDDs.
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