Pasinelli P, Houseweart M K, Brown R H, Cleveland D W
Massachusetts General Hospital-East, Charlestown, MA 02129, USA.
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13901-6. doi: 10.1073/pnas.240305897.
Familial amyotrophic lateral sclerosis-linked mutations in copper-zinc superoxide dismutase cause motor neuron death through one or more acquired toxic properties. An early event in the mechanism of toxicity from such mutants is now demonstrated to be activation of caspase-1. Neuronal death, however, follows only after months of chronic caspase-1 activation concomitantly with activation of the executioner caspase-3 as the final step in the toxic cascade. Thus, a common toxicity of mutant SOD1 is a sequential activation of at least two caspases, caspase-1 that acts slowly as a chronic initiator and caspase-3 acting as the final effector of cell death.
与家族性肌萎缩侧索硬化相关的铜锌超氧化物歧化酶突变通过一种或多种获得性毒性特性导致运动神经元死亡。现在已证明，此类突变体毒性机制中的一个早期事件是半胱天冬酶-1的激活。然而，只有在数月的慢性半胱天冬酶-1激活之后，伴随着刽子手半胱天冬酶-3的激活作为毒性级联反应的最后一步，神经元才会死亡。因此，突变型超氧化物歧化酶1的一种常见毒性是至少两种半胱天冬酶的顺序激活，半胱天冬酶-1作为慢性启动子缓慢起作用，而半胱天冬酶-3作为细胞死亡的最终效应器起作用。
