...
首页> 外文期刊>Current drug targets. CNS and neurological disorders >Calpain and its involvement in the pathophysiology of CNS injuries and diseases: therapeutic potential of calpain inhibitors for prevention of neurodegeneration.
【24h】

Calpain and its involvement in the pathophysiology of CNS injuries and diseases: therapeutic potential of calpain inhibitors for prevention of neurodegeneration.

机译:钙蛋白酶及其在中枢神经系统损伤和疾病的病理生理中的作用:钙蛋白酶抑制剂对预防神经变性的治疗潜力。

获取原文
获取原文并翻译 | 示例
           

摘要

Calpain is a Ca(2+)-activated proteolytic enzyme involved in neurodegeneration in a variety of injuries and diseases of the central nervous system (CNS). Many calpain homologs have been discovered. Depending on the tissue distribution, calpains are broadly classified as ubiquitous and tissue-specific. Ubiquitous calpain isoforms, -calpain and m-calpain, are abundantly expressed in the CNS. Calpastatin, an endogenous protein inhibitor, regulates the activity of ubiquitous calpain. Overactivation of calpain may degrade calpastatin, limiting its regulatory efficiency. Molecular structures of calpain and calpastatin have been deduced from cDNA cloning. The precise physiological function of calpain remains elusive. However, experimental evidence strongly suggests an important role for calpain in causing neurodegeneration in various injuries and diseases of the CNS. The increase in intracellular free Ca(2+) levels in the course of injuries and diseases in the CNS causes overactivation of calpain, promoting degradation of key cytoskeletal and membrane proteins. Cleavage of these key proteins by calpain is an irreversible process that perturbs the integrity and stability of CNS cells, leading to programmed cell death or apoptosis. Calpain in conjunction with caspases can cause apoptosis of the CNS cells. An aberrant Ca(2+) homeostasis inevitably activates calpain, which plays a crucial role in the pathophysiology of the CNS injuries and diseases. Therefore, calpain is a potential therapeutic target to prevent neurodegeneration. To this end, various cell-permeable calpain inhibitors have been synthesized for pharmacological inhibition of calpain activity. Some calpain inhibitors have shown significant neuroprotection in animal models of the CNS injuries and diseases, indicating their therapeutic potential.
机译:钙蛋白酶是一种Ca(2+)活化的蛋白水解酶,参与多种中枢神经系统(CNS)的损伤和疾病中的神经变性。已经发现许多钙蛋白酶同源物。取决于组织的分布,钙蛋白酶大致分为普遍存在的和组织特异性的。无处不在的钙蛋白酶同工型,-钙蛋白酶和间-钙蛋白酶在中枢神经系统中大量表达。钙蛋白酶抑制素是一种内源性蛋白抑制剂,可调节普遍存在的钙蛋白酶的活性。钙蛋白酶的过度活化可能会降解钙蛋白酶抑制素,从而限制其调节效率。钙蛋白酶和钙蛋白酶抑制素的分子结构已从cDNA克隆中推导。钙蛋白酶的精确生理功能仍然难以捉摸。然而,实验证据强烈表明钙蛋白酶在引起各种中枢神经系统损伤和疾病的神经退行性变中起重要作用。在中枢神经系统损伤和疾病过程中细胞内游离Ca(2+)水平的增加导致钙蛋白酶的过度激活,从而促进关键细胞骨架和膜蛋白的降解。钙蛋白酶对这些关键蛋白的切割是不可逆的过程,会干扰CNS细胞的完整性和稳定性,从而导致程序性细胞死亡或凋亡。钙蛋白酶与胱天蛋白酶结合可导致CNS细胞凋亡。异常的Ca(2+)动态平衡不可避免地激活了钙蛋白酶,钙蛋白酶在中枢神经系统损伤和疾病的病理生理中起着至关重要的作用。因此,钙蛋白酶是预防神经变性的潜在治疗靶标。为此,已经合成了多种可透过细胞的钙蛋白酶抑制剂,以抑制钙蛋白酶活性。一些钙蛋白酶抑制剂在中枢神经系统损伤和疾病的动物模型中显示出明显的神经保护作用,表明它们的治疗潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号