Therapeutic potentials of the Rho kinase inhibitor Fasudil in experimental autoimmune encephalomyelitis and the related mechanisms

• Published in: Metabolic brain disease 2019-04, Vol.34 (2), p.377-384
• Main Authors: Yan, Yuqing, Yu, Jiezhong, Gao, Ye, Kumar, Gajendra, Guo, Minfang, Zhao, Yijin, Fang, Qingli, Zhang, Huiyu, Yu, Jingwen, Jiang, Yuqiang, Zhang, Han-Ting, Ma, Cun-Gen
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; Activation; Alzheimer's disease; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Central nervous system; Cytokines - metabolism; Demyelination; Disease; Encephalomyelitis, Autoimmune, Experimental - diagnosis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Enzyme inhibitors; Experimental allergic encephalomyelitis; Health problems; Humans; Inflammation - drug therapy; Inhibitors; Kinases; Medical treatment; Metabolic Diseases; Movement disorders; Multiple sclerosis; Multiple Sclerosis - diagnosis; Multiple Sclerosis - drug therapy; Neurodegeneration; Neurodegenerative diseases; Neurological diseases; Neurology; Neurosciences; Oncology; Parkinson's disease; Protein Kinase Inhibitors - pharmacology; Review Article; Rho-associated kinase; rho-Associated Kinases - antagonists & inhibitors; Rocks; Signal transduction; Signaling; Substantia alba; Therapeutic applications
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-018-0355-7

Multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurodegenerative diseases of central nervous system (CNS) disorders are serious human health problems. Rho-kinase (ROCK) is emerging as a potentially important therapeutic target relevant to inflammatory neurodegeneration diseases. This is supported by studies showing the beneficial effects of fasudil, a ROCK inhibitor, in inflammatory neurodegeneration diseases. MS is an autoimmune disease resulting from inflammation and demyelination in the white matter of the CNS. It has been postulated that activation of Rho/ROCK causes neuropathological changes accompanied with related clinical symptoms, which are improved by treatment with ROCK inhibitors. Therefore, inhibition of abnormal activation of the Rho/ROCK signaling pathway appears to be a new mechanism for treating CNS diseases. In this review, we extensively discussed the role of ROCK inhibitors, summarized the efficacy of fasudil in the MS conventional animal model of experimental autoimmune encephalomyelitis (EAE), both in vivo and in vitro, and highlighted the mechanism involved. Overall, the findings collected in this review support the role of the ROCK signaling pathway in neurodegenerative diseases. Hence, ROCK inhibitors such as fasudil can be novel, and efficacious treatment for inflammatory neurodegenerative diseases.