The role of caspases in Alzheimer's disease; potential novel therapeutic opportunities
The role of caspases in Alzheimer's disease; potential novel therapeutic opportunities
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DOI：
10.1007/s10495-010-0463-2
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发表时间：
2010-11-01
期刊：
影响因子：
7.2
通讯作者：
Rohn, Troy T.
中科院分区：
文献类型：
--
作者：
Rohn, Troy T.
尽管细胞凋亡在将CNS塑造成其最终外观和功能中起着关键作用，但在衰老脑中该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，大量证据支持细胞凋亡的激活，特别是半胱天冬酶的激活作为早期事件，其不仅可能导致神经变性，而且还促进与这种疾病相关的潜在病理学。因此，半胱天冬酶抑制剂可能为治疗AD提供一种有效的策略。然而，尽管有令人信服的证据表明半胱天冬酶在疾病进展中的作用，但在AD动物模型中从未进行过半胱天冬酶抑制剂的长期治疗。在这篇综述中，半胱天冬酶在AD中的作用将得到解决，包括最近的研究利用体内转基因小鼠模型的tau蛋白病。此外，还将评估使用半胱天冬酶抑制剂（如Q-VD-OPh）治疗AD时靶向半胱天冬酶抑制的治疗价值和危险性。
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.