Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (12): 2623-2631.doi: 10.4103/1673-5374.335827

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

Qing Wang1, Li-Juan Song1, 2, Zhi-Bin Ding1, Zhi Chai1, Jie-Zhong Yu3, 4, Bao-Guo Xiao1, 5, *, Cun-Gen Ma1, 3, *   

  1. 1Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong, Shanxi Province, China; 2Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi Province, China; 3Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong, Shanxi Province, China; 4Department of Neurology, Datong Fifth People’s Hospital, Datong, Shanxi Province, China; 5Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Cun-Gen Ma, PhD, macungen@sxtcm.edu.cn; Bao-Guo Xiao, PhD, bgxiao@shmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81473577 (to CGM), 81903596 (to QW), 82004028 (to LJS); China Postdoctoral Science Foundation, No. 2020M680912 (to LJS); Open Project of The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education of China,No. 2019004 (to CGM); Science and Technology Innovation Project of Shanxi Colleges of China, Nos. 2019L0728 (to QW); and Cultivation Project of Shanxi Universtity of Chinese Medicine of China, No. 2019PY130 (to QW).

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Abstract: 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.

Key words: Alzheimer’s disease, cell-based therapy, central nervous system cells, fasudil, immunocytes, multiple sclerosis, Parkinson’s disease, pericytes, Rho kinase inhibitor, Rho-associated kinases