Bevers Matthew B, Neumar Robert W
Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
J Cereb Blood Flow Metab. 2008 Apr;28(4):655-73. doi: 10.1038/sj.jcbfm.9600595. Epub 2007 Dec 12.
The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular locations are explored. Calpain substrates within synapses, plasma membrane, endoplasmic reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall effect of postischemic calpain activity on calcium regulation and cell death signaling are considered. Finally, potential pathways for calpain-mediated neurodegeneration are outlined in an effort to guide future studies aimed at understanding the downstream pathology of postischemic calpain activity and identifying optimal therapeutic strategies.
蛋白酶的钙蛋白酶家族与缺血后神经变性存在因果关联。然而，钙蛋白酶导致缺血后神经元死亡的确切机制尚未完全阐明。本综述概述了钙蛋白酶系统的关键特征，以及其在缺血后神经元病理中因果作用的证据。此外，还探讨了在不同亚细胞位置特异性切割钙蛋白酶底物的后果。考虑了突触、质膜、内质网、溶酶体、线粒体和细胞核内的钙蛋白酶底物，以及缺血后钙蛋白酶活性对钙调节和细胞死亡信号传导的总体影响。最后，概述了钙蛋白酶介导的神经变性的潜在途径，以指导未来旨在了解缺血后钙蛋白酶活性下游病理并确定最佳治疗策略的研究。
