ROCK2 inhibition: A futuristic approach for the management of Alzheimer's disease

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

Research output: Contribution to journalComment/debatepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article number104871
JournalNeuroscience and Biobehavioral Reviews
Volume142
DOIs
Publication statusPublished - Nov 2022

Keywords

  • Alzheimer's disease
  • Mitochondria
  • Mitophagy
  • Neurodegeneration
  • Neuroprotection
  • Parkin
  • ROCK

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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