Wang Yubin, Bi Xiaoning, Baudry Michel
a Graduate College of Biomedical Sciences , Western University of Health Sciences , Pomona , CA , USA.
b Department of Basic Science , COMP, Western University of Health Sciences , Pomona , CA , USA.
Expert Opin Ther Targets. 2018 Jan;22(1):19-29. doi: 10.1080/14728222.2018.1409723. Epub 2017 Nov 28.
Calpains represent a family of neutral, calcium-dependent proteases, which modify the function of their target proteins by partial truncation. These proteases have been implicated in numerous cell functions, including cell division, proliferation, migration, and death. In the CNS, where calpain-1 and calpain-2 are the main calpain isoforms, their activation has been linked to synaptic plasticity as well as to neurodegeneration. This review will focus on the role of calpain-2 in acute neuronal injury and discuss the possibility of developing selective calpain-2 inhibitors for therapeutic purposes. Areas covered: This review covers the literature showing how calpain-2 is implicated in neuronal death in a number of pathological conditions. The possibility of developing new selective calpain-2 inhibitors for treating these conditions is discussed. Expert opinion: As evidence accumulates that calpain-2 activation participates in acute neuronal injury, there is interest in developing therapeutic approaches using selective calpain-2 inhibitors. Recent data indicate the potential use of such inhibitors in various pathologies associated with acute neuronal death. The possibility of extending the use of such inhibitors to more chronic forms of neurodegeneration is discussed.
钙蛋白酶是一类中性的、钙依赖性蛋白酶，它们通过部分截短来改变其靶蛋白的功能。这些蛋白酶参与了众多细胞功能，包括细胞分裂、增殖、迁移和死亡。在中枢神经系统中，钙蛋白酶-1和钙蛋白酶-2是主要的钙蛋白酶亚型，它们的激活与突触可塑性以及神经退行性变有关。本综述将聚焦于钙蛋白酶-2在急性神经元损伤中的作用，并探讨开发用于治疗目的的选择性钙蛋白酶-2抑制剂的可能性。涵盖领域：本综述涵盖了相关文献，展示了钙蛋白酶-2在多种病理状况下如何与神经元死亡相关。还讨论了开发新型选择性钙蛋白酶-2抑制剂来治疗这些病症的可能性。专家观点：随着越来越多的证据表明钙蛋白酶-2的激活参与急性神经元损伤，人们对使用选择性钙蛋白酶-2抑制剂开发治疗方法产生了兴趣。近期数据表明此类抑制剂在与急性神经元死亡相关的各种病理状况中的潜在用途。还讨论了将此类抑制剂的使用扩展到更慢性神经退行性变形式的可能性。
