Rho/ROCK2通路在阿尔茨海默病病理进程中的重要作用

Important role of Rho/ROCK2 pathway in the development of Alzheimer′s disease

Rho/Rho相关卷曲螺旋形成蛋白激酶(ROCK)通路是生物体中广泛存在的经典信号通路,参与多种生理调节过程。ROCK有2种亚型,即ROCK1和ROCK2。在阿尔茨海默病(AD)患者脑中,Rho/ROCK2表现为活性上调,并伴有Aβ42水平升高,以及神经细胞突起的形态与功能异常,推测AD的发生、发展与Rho或ROCK2的高表达或过度激活有关。目前Rho/ROCK2通路被认为是预防和治疗AD的一个有效的靶通路,而Rho或ROCK2,也成为药物研发的重要靶点。研究发现,降低Rho或ROCK2的表达,或者抑制Rho或ROCK2的活性均可减少Aβ42诱导的神经毒性,保护神经元,减缓AD的发展。因此,Rho/ROCK2的特异性抑制对中枢神经损伤修复及AD的治疗有重要的意义。为此,本文针对Rho/ROCK2通路在阿尔茨海默病发展中的作用做一综述。

Rho/ROCK pathway is a ubiquitous singling pathway in organisms, and is involved in many biological processes. In the brain of Alzheimer＇s patients, the activities of Rho and Rho associated coiled coil forming protein kinase （ROCK） are up-regulated, which is accompanied by the elevation of Aβ42 level, and the abnormal change of the morphology and function of neuronal processes, suggesting that the occurrence and development of Alzheimer＇s disease （AD） is associafed with the overexpression and excessive activation of Rho or ROCK. Rho/ROCK2 pathway is considered a target pathway for the prevention and treatment of AD, and Rho or ROCK2 also becomes an important target for AD drug development. Numerous studies have revealed that suppressing the expression or decreasing the activity of Rho or ROCK2 can reduce Aβ42-induced neurotoxicity, protect neurons, and slow down the occurrence and development of AD. Therefore, specific inhibition of ROCK2 has an important significance for the repair of central nervous system damage and the treatment of AD. This article reviews several effects of Rho/ROCK2 pathway on the development of AD.