Kudelova J, Fleischmannova J, Adamova E, Matalova E
Hospital Na Bulovce, Prague, Czech Republic.
Institute of Animal Physiology and Genetics, CAS, v.v.i., Brno, Czech Republic.
J Physiol Pharmacol. 2015 Aug;66(4):473-82.
Caspases are key molecules of apoptosis and the inflammatory response. Up-regulation of the caspase cascade contributes to human pathologies such as neurodegenerative and immune disorders. Thus, blocking the excessive apoptosis by pharmacological inhibitors seems promising for therapeutic interventions in such diseases. Caspase inhibitors, both natural and artificial, have been used as research tools and have helped to define the role of the individual caspases in apoptosis and in non-apoptotic processes. Moreover, some caspase inhibitors have demonstrated their therapeutic efficiency in the reduction of cell death and inflammation in animal models of human diseases. However, no drug based on caspase inhibition has been approved on the market until now. Thus, the development of therapeutic approaches that specifically target caspases remains a great challenge and is now the focus of intense biological and clinical interest. Here, we provide a brief review of recent knowledge about pharmacological caspase inhibitors with special focus on their proposed clinical applications.
半胱天冬酶是细胞凋亡和炎症反应的关键分子。半胱天冬酶级联反应的上调会导致人类疾病,如神经退行性疾病和免疫紊乱。因此,通过药理学抑制剂阻断过度的细胞凋亡似乎有望用于此类疾病的治疗干预。天然和人工合成的半胱天冬酶抑制剂都已被用作研究工具,并有助于确定各个半胱天冬酶在细胞凋亡和非凋亡过程中的作用。此外,一些半胱天冬酶抑制剂已在人类疾病动物模型中证明了它们在减少细胞死亡和炎症方面的治疗效果。然而,迄今为止,尚无基于半胱天冬酶抑制的药物获批上市。因此,开发特异性靶向半胱天冬酶的治疗方法仍然是一个巨大的挑战,并且目前是生物学和临床研究的热点。在此,我们简要综述了有关药理学半胱天冬酶抑制剂的最新知识,特别关注其拟议的临床应用。