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

Neural Regeneration Research 2022年第12期17卷 2623-2631页

作者： Qing Wang Li-Juan Song Zhi-Bin Ding Zhi Chai Jie-Zhong Yu Bao-Guo Xiao Cun-Gen Ma Research 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 MedicineShanxi University of Chinese MedicineJinzhongShanxi ProvinceChina Department of Physiology Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Institute of Brain Science Shanxi Key Laboratory of Inflammatory Neurodegenerative DiseasesShanxi Datong UniversityDatongShanxi ProvinceChina Department of Neurology Datong Fifth People’s HospitalDatongShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

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.

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

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