Bilsland James, Harper Sarah
Department of Biochemistry and Molecular Biology, Merck, Sharp and Dohme Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK.
Curr Opin Investig Drugs. 2002 Dec;3(12):1745-52.
Apoptotic cell death has been implicated in the pathogenesis of both acute and chronic neurodegenerative disorders. The caspase family of cysteine proteases are involved both in the initiation and final execution of apoptosis. Inhibition of the caspase family prevents cell death in a number of models of neurodegenerative cell death in vivo and in vitro. This sparing of neurons does not always correlate with long-term functional recovery, possibly due to the limitations of the available inhibitors. In this review, the evidence for a neuroprotective role of caspase inhibition in models of Parkinson's disease and cerebral ischemia is critically evaluated.
凋亡性细胞死亡与急慢性神经退行性疾病的发病机制均有关联。半胱氨酸蛋白酶的半胱天冬酶家族参与了细胞凋亡的起始和最终执行过程。在体内和体外的多种神经退行性细胞死亡模型中,对半胱天冬酶家族的抑制可防止细胞死亡。这种对神经元的保护并不总是与长期功能恢复相关,这可能是由于现有抑制剂存在局限性。在本综述中,我们对在帕金森病和脑缺血模型中半胱天冬酶抑制的神经保护作用的证据进行了批判性评估。