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首页> 外文期刊>Current medicinal chemistry-Anti-inflammatory & anti-allergy agents.Anti-inflammatory & anti-allergy agents >Pharmacological Modulation of Caspase Activation
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Pharmacological Modulation of Caspase Activation

机译：半胱天冬酶激活的药理调制

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摘要

Deregulation of apoptosis resulting either in inappropriate loss or accumulation of cells is a major cause of many severe pathological conditions such as cancer, autoimmune diseases, microbial infections and degenerative disorders. Consequently, great interest has emerged in devising therapeutic strategies for intervening with cell death, either in a pro- or antiapoptotic direction. Among the different apoptosis-based drug targets, caspases, a family of intracellular cys-teine proteases are most promising candidates, because they form the central core of the apoptotic machinery that coordinate cell death from various signals. Inappropriate cell death can be efficiently blocked by caspase inhibitors, whereas caspase activation or the inhibition of endogenous caspase inhibitors might be useful for the eradication of unwanted cells. Currently, numerous novel approaches are being followed employing gene therapy, antisense strategies, recombinant biologies or organic chemistry in order to target caspases or their endogenous inhibitors. Exciting proof-of-principle evidence obtained in several animal models confirms the validity of strategies targeting caspases and their enormous therapeutic potential. Although mostly in preclinical state, several therapeutics have recently progressed to clinical testing or were even approved by drug administration. This review summarizes the recent advances in the field of caspase targeting and discusses its wide-ranging opportunities for different human diseases.
机译：在放松管制而导致的细胞凋亡不恰当的或积累的细胞是一个损失许多严重的病态的主要原因条件如癌症、自身免疫性疾病微生物感染和退行性疾病。因此,出现了极大的兴趣制定治疗干预策略细胞死亡,在赞成或凋亡方向。还存在apoptosis-based药物靶点,,一个家庭胞内cys-teine蛋白酶的最多有希望的候选人,因为它们形成了凋亡机制的核心协调不同信号的细胞死亡。不合适可以有效的细胞死亡被半胱天冬酶抑制剂,而半胱天冬酶激活或抑制内源性半胱天冬酶抑制剂可能是有用的消除不需要的细胞。许多新方法正被人跟踪使用基因疗法,反义策略,重组生物学或有机化学为了目标还存在或其内生抑制剂。在一些动物模型证实了针对还存在和有效性的策略他们的巨大的治疗潜力。主要在临床前的状态,几个疗法最近发展到临床测试或甚至药品管理局批准。的最新进展作一综述半胱天冬酶定位领域,并讨论它广泛的不同的人的机会疾病。

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