ROCK2 inhibition: A futuristic approach for the management of Alzheimer's disease. (November 2022)

• Record Type: Journal Article
• Authors: Mani, Shalini; Jindal, Divya; Chopra, Hitesh; Jha, Saurabh Kumar; Singh, Sachin Kumar; Ashraf, Gulam Md; Kamal, Mehnaz; Iqbal, Danish; Chellappan, Dinesh Kumar; Dey, Abhijit; Dewanjee, Saikat; Singh, Keshav K.; Ojha, Shreesh; Singh, Inderbir; Gautam, Rupesh K.; Jha, Niraj Kumar
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 142(2022)
• Publication Date: 2022-11
• Subjects: Neurodegeneration -- Alzheimer's disease -- ROCK -- Mitophagy -- Parkin -- Mitochondria -- Neuroprotection; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2022.104871
• Languages: English
• ISSNs: 0149-7634

Abstract

Abstract: 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. Graphical Abstract: ga1 Highlights: Mitophagy disruption in neurons is implicated in Alzheimer's disease (AD). The process of mitophagy is observed to be disrupted in different neuronal cells, leading to a variety of pathogenic circumstances. Triggering mitophagy seems to be a promising therapeutic strategy for the treatment of AD. ROCK2 inhibits Parkin-dependent mitophagy and it is suggested to negatively regulate the Parkin-dependent mitophagy pathway. ROCK2 inhibition may therefore be a promising therapeutic approach.