Cho Benjamin B, Toledo-Pereyra Luis H
Michigan State University, College of Human Medicine, Kalamazoo, MI 49008, USA.
J Invest Surg. 2008 May-Jun;21(3):141-7. doi: 10.1080/08941930802029945.
There is accumulating evidence that caspase-independent programs play a significant role in delayed neuronal death following ischemic stroke. Previous research has implicated mitochondrial proteins, such as apoptosis-inducing factor (AIF) and Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP3), as players involved in this pathway. More recent work has begun to hone in on the specific interactions between these molecules and the mediators that might function upstream [e.g., poly(ADP-ribose) polymerase-1 (PARP-1)] and downstream [e.g., endonuclease G (EndoG)] of them. As the study of caspase-independent programs has expanded, it has become increasingly apparent that this pathway is not simply an alternative to apoptosis when caspases are unavailable, but a unique process, distinct from both apoptosis and necrosis. Similar caspase-independent pathways as the ones mentioned apply to organ systems outside of the central nervous system. Put together, the data suggest that caspase-independent programmed cell death is a complex and resilient death program that will likely need to be considered and countered in devising an effective drug therapy for the treatment of ischemic stroke.
越来越多的证据表明，不依赖半胱天冬酶的程序在缺血性中风后的迟发性神经元死亡中起重要作用。先前的研究表明，线粒体蛋白，如凋亡诱导因子（AIF）和Bcl-2/腺病毒E1B 19 kDa相互作用蛋白（BNIP3），参与了这一途径。最近的研究开始关注这些分子与可能在其上游[如聚（ADP-核糖）聚合酶-1（PARP-1）]和下游[如核酸内切酶G（EndoG）]起作用的介质之间的具体相互作用。随着对不依赖半胱天冬酶程序的研究不断扩展，越来越明显的是，这条途径不仅仅是在半胱天冬酶无法发挥作用时凋亡的替代途径，而是一个独特的过程，与凋亡和坏死都不同。上述类似的不依赖半胱天冬酶的途径也适用于中枢神经系统以外的器官系统。综合来看，数据表明不依赖半胱天冬酶的程序性细胞死亡是一个复杂且有弹性的死亡程序，在设计治疗缺血性中风的有效药物疗法时，可能需要考虑并应对这一程序。
