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

  • Yuqing Yan
  • Jiezhong Yu
  • Ye Gao
  • Gajendra Kumar
  • Minfang Guo
  • Yijin Zhao
  • Qingli Fang
  • Huiyu Zhang
  • Jingwen Yu
  • Yuqiang JiangEmail author
  • Han-Ting ZhangEmail author
  • Cun-Gen MaEmail author
Review Article


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.


Rho-kinase Fasudil Experimental autoimmune encephalomyelitis Microglia/macrophages Multiple sclerosis 



This work was supported by grants from the National Natural Science Foundation of China (No. 81272163 to CGM, 81471412 to JZY and 81371414 to CGM), the Department of Science and Technology, Shanxi Province of China (2016ZD0505 to JZY, HQXTCXZX2016-022 to JWY), Datong Municipal Science and Technology Bureau (No.2017134 to YQY), PhD initiation Grant of Datong University (No. 2016-B-01 to YQY, 2017-B-23 to Y G), and Open project of State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China(2018-MDB-KF-07 to YQY).

Author contribution

YY and JY outlined and drafted the manuscript. CGM, HTZ and YJ helped coordinate and draft the manuscript. YG, MG, GK, YZ, QF, HZ, JY were involved in the revisions. HTZ and CGM revised and finalized the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests. None of the authors has any potential financial conflict of interest related to this manuscript.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yuqing Yan
    • 1
  • Jiezhong Yu
    • 1
    • 2
  • Ye Gao
    • 1
  • Gajendra Kumar
    • 3
  • Minfang Guo
    • 1
  • Yijin Zhao
    • 1
  • Qingli Fang
    • 1
  • Huiyu Zhang
    • 1
  • Jingwen Yu
    • 1
  • Yuqiang Jiang
    • 2
    Email author
  • Han-Ting Zhang
    • 1
    • 4
    Email author
  • Cun-Gen Ma
    • 1
    • 5
    Email author
  1. 1.Institute of Brain ScienceShanxi Datong UniversityDatongChina
  2. 2.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina
  3. 3.Department of Biomedical SciencesCity University of Hong KongTat Chee AvenueHong Kong
  4. 4.Departments of Behavioral Medicine & Psychiatry, Physiology & Pharmacology, and Neuroscience, the Rockefeller Neurosciences InstituteWest Virginia University Health Sciences CenterMorgantownUSA
  5. 5.“2011” Collaborative Innovation Center/Research Center of NeurobiologyTaiyuanChina

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