, Volume 24, Issue 2, pp 117-123
Date: 22 May 2008

Mechanisms of lysosomal proteases participating in cerebral ischemia-induced neuronal death

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Abstract

There are three different types of cell death, including apoptosis (Type I), autophagic cell death (Type II), and necrosis (Type III). Ischemic neuronal death influences stroke development and progression. Lysosomes are important organelles having an acidic milieu to maintain cellular metabolism by degrading unneeded extra-and intracellular substances. Lysosomal enzymes, including cathepsins and some lipid hydrolases, when secreted following rupture of the lysosomal membrane, can be very harmful to their environment, which results in pathological destruction of cellular structures. Since lysosomes contain catalytic enzymes for degrading proteins, carbohydrates and lipids, it seems natural that they should participate in cellular death and dismantling. In this review, we discuss the recent developments in ischemic neuronal death, and present the possible molecular mechanisms that the lysosomal enzymes participate in the three different types of cell death in ischemic brain damage. Moreover, the research related to the selective cathepsin inhibitors may provide a novel therapeutic target for treating stroke and promoting recovery.

摘要

细胞死亡有凋亡(I 型)、自噬性细胞死亡(II 型)和坏死(III 型) 三种方式. 缺血性神经元的死亡影响着中风的发展进程. 溶酶体是一种重要的细胞器, 通过在酸性环境中降解不需要的胞外和胞内物质来维持细胞代谢的稳态. 溶酶体酶包括组织蛋白酶和脂质水解酶, 当溶酶体膜破裂时它们会被释放到细胞浆, 会对细胞内环境产生危害, 最终导致细胞结构的破坏. 由于溶酶体含有催化蛋白、碳水化合物和脂质的酶, 因此它们参与细胞的死亡看起来是情理之中的事情. 本综述讨论了缺血性神经元死亡的最新进展, 指出在缺血性脑损伤中溶酶体酶参与三种细胞死亡方式的可能的分子机制, 同时指出了选择性的组织蛋白酶抑制剂可能是治疗中风和促进康复新的治疗靶点.