Yan-Le Xin, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University
Jie-Zhong Yu, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong UniversityFollow
Xin-Wang Yang, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University
Chun-Yun Liu, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University
Yan-Hua Li, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong UniversityFollow
Ling Feng, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University
Zhi Chai, 2011 Collaborative Innovation Center, Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine
Wan-Fang Yang, 2011 Collaborative Innovation Center, Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine
Qing Wang, 2011 Collaborative Innovation Center, Research Center of Neurobiology, Shanxi University of Traditional Chinese MedicineFollow
Wei-Jia Jiang, 2011 Collaborative Innovation Center, Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine
Guang-Xian Zhang, Department of Neurology, Thomas Jefferson UniversityFollow
Bao-Guo Xiao, Institute of Neurology, Huashan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Fudan UniversityFollow
Cun-Gen Ma, Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University; 2011 Collaborative Innovation Center, Research Center of Neurobiology, Shanxi University of Traditional Chinese MedicineFollow

Document Type

Article

Publication Date

10-1-2015

Comments

This article has been peer reviewed. It was published in: Bioscience Reports.

Volume 35, Issue 5, 1 October 2015, Article number e00247.

The published version is available at DOI: 10.1042/BSR20150032

Copyright © 2015 Authors.

Abstract

Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and vasodilation between Fasudil and FSD-C10. The results demonstrated that FSD-C10, like Fasudil, induced neurite outgrowth of neurons and dendritic formation of BV-2 microglia and enhanced the production of neurotrophic factor brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3). However, the cell cytotoxicity and vasodilation of FSD-C10 were relatively small compared with Fasudil. Although Fasudil inhibited both ROCK I and ROCK II, FSD-C10 more selectively suppressed ROCK II, but not ROCK I, which may be related to vasodilation insensitivity and animal mortality. Thus, FSD-C10 may be a safer and more promising novel ROCK inhibitor than Fasudil for the treatment of several neurological disorders.

PubMed ID

26223433

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