Department of Biology, Boise State University, Science/Nursing Building, Room 228, Boise, Idaho 83725, USA.
Apoptosis. 2010 Nov;15(11):1403-9. doi: 10.1007/s10495-010-0463-2.
Although apoptosis plays a critical role in molding the CNS into its final appearance and function, inappropriate activation of this pathway in the aging brain may contribute to neurodegeneration. In Alzheimer's disease (AD), an overwhelming body of evidence supports the activation of apoptosis in general, and caspases specifically as an early event that may not only contribute to neurodegeneration but also promote the underlying pathology associated with this disease. Therefore, caspase inhibitors may provide an effective strategy for treating AD. However, despite the compelling evidence indicating a role for caspases in disease progression, chronic treatment with caspase inhibitors in animal models of AD has never been undertaken. In this review the role of caspases in AD will be addressed, including recent studies utilizing in vivo transgenic mouse models of tauopathies. In addition, a discussion of the therapeutic value and dangers of targeting caspase inhibition in the treatment of AD using caspase inhibitors such as Q-VD-OPh will be evaluated.
尽管细胞凋亡在塑造中枢神经系统的最终形态和功能方面起着关键作用，但在衰老大脑中，这条途径的不适当激活可能导致神经退行性变。在阿尔茨海默病（AD）中，大量证据支持凋亡的普遍激活，特别是半胱氨酸天冬氨酸蛋白酶（caspases）作为一个早期事件，不仅可能导致神经退行性变，而且可能促进与该疾病相关的潜在病理学。因此，半胱氨酸天冬氨酸蛋白酶抑制剂可能为治疗 AD 提供一种有效策略。然而，尽管有令人信服的证据表明半胱氨酸天冬氨酸蛋白酶在疾病进展中的作用，但在 AD 的动物模型中从未进行过慢性半胱氨酸天冬氨酸蛋白酶抑制剂治疗。在这篇综述中，将讨论半胱氨酸天冬氨酸蛋白酶在 AD 中的作用，包括利用体内转基因小鼠 tau 病模型的最近研究。此外，还将评估使用半胱氨酸天冬氨酸蛋白酶抑制剂（如 Q-VD-OPh）靶向半胱氨酸天冬氨酸蛋白酶抑制作为 AD 治疗的治疗价值和危险。
