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首页> 外文期刊>CNS drug reviews >Involvement of calpain activation in neurodegenerative processes.
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Involvement of calpain activation in neurodegenerative processes.

机译：钙蛋白酶激活参与神经变性过程。

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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 beta-amyloid or 3-nitropropionic 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.
机译：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，以开发用于治疗神经退行性疾病的适当药物为目标。胱天蛋白酶和钙蛋白酶是在脑部疾病中最典型的半胱氨酸蛋白酶。同样，在过去的十年中，广泛的研究表明，钙蛋白酶活性的失调是多种神经退行性疾病中的关键细胞毒性事件。而且，由于cdk5参与神经退行性疾病，因此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受局部缺血的侵害，还可以预防由β-淀粉样蛋白或3-硝基丙酸等神经毒素引起的神经毒性，因此目前可获得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。显然，半胱氨酸蛋白酶的不适当活化不仅发生在神经元细胞死亡期间，而且还可能导致局部缺血和外伤性脑部疾病的脑病理。因此，钙蛋白酶激活的药理学调节可用于治疗神经退行性疾病。尽管有困难，但有可能开发出半胱氨酸蛋白酶，特别是钙蛋白酶的合成抑制剂。最近，对钙蛋白酶激活的抑制已成为治疗神经退行性疾病的潜在治疗靶标。

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