Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases

Autor: Qing Wang, Li-Juan Song, Zhi-Bin Ding, Zhi Chai, Jie-Zhong Yu, Bao-Guo Xiao, Cun-Gen Ma
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Neural Regeneration Research, Vol 17, Iss 12, Pp 2623-2631 (2022)
Druh dokumentu: article
ISSN: 1673-5374
DOI: 10.4103/1673-5374.335827
Popis: Ras homolog (Rho)-associated kinases (ROCKs) belong to the serine-threonine kinase family, which plays a pivotal role in regulating the damage, survival, axon guidance, and regeneration of neurons. ROCKs are also involved in the biological effects of immune cells and glial cells, as well as the development of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Previous studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation, regulating immune imbalance, repairing the blood-brain barrier, and promoting nerve repair and myelin regeneration. Fasudil, the first ROCKs inhibitor to be used clinically, has a good therapeutic effect on neurodegenerative diseases. Fasudil increases the activity of neural stem cells and mesenchymal stem cells, thus optimizing cell therapy. This review will systematically describe, for the first time, the effects of abnormal activation of ROCKs on T cells, B cells, microglia, astrocytes, oligodendrocytes, and pericytes in neurodegenerative diseases of the central nervous system, summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases, and clarify the possible cellular and molecular mechanisms of ROCKs inhibition. This review also proposes that fasudil is a novel potential treatment, especially in combination with cell-based therapy. Findings from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.
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