Bartus R T, Elliott P J, Hayward N J, Dean R L, Harbeson S, Straub J A, Li Z, Powers J C
Alkermes, Inc., Cambridge, MA 02139, USA.
Neurol Res. 1995 Aug;17(4):249-58. doi: 10.1080/01616412.1995.11740322.
Calpains are cytosolic, neutral proteases that normally exist in an inactive or quiescent state. They require higher than normal levels of calcium for activation which, once accomplished, lead to irreversible proteolysis of numerous cytoskeletal, membrane-associated and regulatory proteins. Because of these characteristics, calpain is gaining attention as a potentially important pathogenic variable in ischemic neuronal death. This manuscript explores this hypothesis by briefly reviewing current support for the role played by calpain in ischemic neurodegeneration, and then discussing a series of recently published studies which: 1. offer further evidence for the hypothesis, and 2. provide direct support for the idea that selective inhibition of calpain can greatly limit the neuronal damage that would normally occur following both global as well as focal brain ischemia. Thus, the data reviewed in this manuscript support the ideas that unregulated activation and proteolysis of intraneuronal calpain plays a significant role in the brain damage that occurs following an ischemic event and that delivering selective and membrane permeant calpain inhibitors to ischemic tissue may provide a powerfully effective therapeutic means of limiting neuronal damage.
钙蛋白酶是一种胞质中性蛋白酶，通常以无活性或静止状态存在。它们需要高于正常水平的钙来激活，一旦激活，就会导致众多细胞骨架、膜相关和调节蛋白发生不可逆的蛋白水解。由于这些特性，钙蛋白酶作为缺血性神经元死亡中一个潜在的重要致病变量而受到关注。本文通过简要回顾目前关于钙蛋白酶在缺血性神经退行性变中所起作用的支持证据，然后讨论一系列最近发表的研究来探讨这一假设，这些研究：1. 为该假设提供了进一步的证据，2. 直接支持了选择性抑制钙蛋白酶可以极大地限制在全脑以及局灶性脑缺血后通常会发生的神经元损伤这一观点。因此，本文所回顾的数据支持以下观点：神经元内钙蛋白酶的无节制激活和蛋白水解在缺血事件后发生的脑损伤中起重要作用，并且向缺血组织递送选择性且能透过膜的钙蛋白酶抑制剂可能提供一种极其有效的治疗手段来限制神经元损伤。
