Involvement of calpain activation in neurodegenerative processes
Involvement of calpain activation in neurodegenerative processes
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DOI：
10.1111/j.1527-3458.2006.00135.x
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发表时间：
2006-06-01
期刊：
影响因子：
--
通讯作者：
Pallas, Merce
中科院分区：
文献类型：
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作者：
Camins, Antoni;Verdaguer, Ester;Pallas, Merce
未来几年的挑战之一将是更好地了解神经元细胞死亡的机制，以开发足够的药物来治疗神经退行性疾病。半胱天冬酶和钙蛋白酶是在大脑疾病中激活的最具特征的半胱氨酸蛋白酶。同样，在过去十年中，广泛的研究表明，calpain活性的解除是各种神经退行性疾病的关键细胞毒性事件。此外，由于cdk5参与神经退行性疾病的暗示，对钙蛋白酶在神经退行性过程中的作用的兴趣正在增长。由于钙蛋白酶抑制剂似乎不仅可以保护脑组织免于缺血，而且还可以防止p -淀粉样蛋白或3-硝基丙离子酸等神经毒素引起的神经毒性，目前可用的数据表明，钙蛋白酶和cdk5在神经元细胞死亡中起关键作用。似乎很清楚，半胱氨酸蛋白酶的不适当激活不仅发生在神经元细胞死亡期间，而且可能导致脑缺血和创伤性脑疾病的脑病理。因此，钙蛋白酶激活的药理调节可能对神经退行性疾病的治疗有用。开发半胱氨酸蛋白酶的合成抑制剂，特别是钙蛋白酶，是可能的，尽管困难重重。抑制钙蛋白酶的激活最近成为治疗神经退行性疾病的潜在治疗靶点。
One of the challenges in the coming years will be to better understand the mechanisms of neuronal cell death with the objective of developing adequate drugs for the treatment of neurodegenerative disorders. Caspases and calpains are among the best-characterized cysteine proteases activated in brain disorders. Likewise, during the last decade, extensive research revealed that the deregulation of calpains activity is a key cytotoxic event in a variety of neurodegenerative disorders. Moreover, interest in the role of calpain in neurodegenerative processes is growing due to implication of the involvement of cdk5 in neurodegenerative diseases. Since calpain inhibitors appear to not only protect brain tissue from ischemia, but also to prevent neurotoxicity caused by such neurotoxins as P-amyloid or 3-nitroprop ionic acid, the currently available data suggest that calpain and cdk5 play a key role in neuronal cell death. It seems clear that the inappropriate activation of cysteine proteases occurs not only during neuronal cell death, but may also contribute to brain pathology in ischemia and traumatic brain disorders. Pharmacological modulation of calpain activation may, therefore, be useful in the treatment of neurodegenerative disorders. It is possible, although difficult, to develop synthetic inhibitors of cysteine proteases, specifically calpains. The inhibition of calpain activation has recently emerged as a potential therapeutic target for the treatment of neurodegenerative diseases.