Olson Michael F
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Curr Opin Cell Biol. 2008 Apr;20(2):242-8. doi: 10.1016/j.ceb.2008.01.002. Epub 2008 Feb 20.
ROCK kinases, which play central roles in the organization of the actin cytoskeleton, are tantalizing targets for the treatment of human diseases. Deletion of ROCK I in mice revealed a role in the pathophysiological responses to high blood pressure, and validated ROCK inhibition for the treatment of specific types of cardiovascular disease. To date, the only ROCK inhibitor employed clinically in humans is fasudil, which has been used safely in Japan since 1995 for the treatment of cerebral vasospasm. Clinical trials, mostly focusing on the cardiovascular system, have uncovered beneficial effects of fasudil for additional indications. Intriguing recent findings also suggest significant potential for ROCK inhibitors in the production and implantation of stem cells for disease therapies.
ROCK激酶在肌动蛋白细胞骨架的组织中发挥核心作用,是治疗人类疾病极具吸引力的靶点。小鼠体内ROCK I的缺失揭示了其在高血压病理生理反应中的作用,并验证了ROCK抑制在治疗特定类型心血管疾病中的作用。迄今为止,临床上唯一用于人类的ROCK抑制剂是法舒地尔,自1995年以来它在日本已被安全用于治疗脑血管痉挛。主要针对心血管系统的临床试验发现法舒地尔对其他适应症也有有益作用。最近有趣的研究结果还表明,ROCK抑制剂在用于疾病治疗的干细胞生产和植入方面具有巨大潜力。