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首页> 外文期刊>Current drug targets. CNS and neurological disorders >Natural and synthetic inhibitors of caspases: targets for novel drugs.
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Natural and synthetic inhibitors of caspases: targets for novel drugs.

机译：胱天蛋白酶的天然和合成抑制剂：新药的靶标。

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Along with inflammation, apoptosis appears a common feature of cell death in non-infectious neurodegenerative diseases. The apoptotic program is an energy-requiring, slowly developing process that evolves in three main steps; initiation, progression and execution. Each step of the program is controlled by a number of molecules with synergistic or antagonistic functions, among which the family of cystein proteases called caspases has a primary role. The central position of caspases in all steps of the apoptotic process had led to the development of several families of inhibitory drugs based on the tetrapeptidic sequence of their preferred cleavage site on target molecules. The initial classes of compounds had problems of toxicity, specificity and blood brain barrier penetration, but even so, gave encouraging preclinical results in animal models of neurological diseases. New generations of anti-caspase drugs have been developed, including non peptide-based compounds, which have shown satisfactory pharmaceutical activity. In addition, pre-clinical developments include advances in protein therapy based on the use of natural inhibitors of caspases, which possess the advantage of targeting synergistic neuroprotective pathways. This strategy uses peptidic vectors to carry large molecules through the blood brain barrier and the membrane of brain cells. Although pre-clinical data are compelling, the activity of these various drug families in patients with acute and/or progressive brain lesions has yet to be demonstrated.
机译：除炎症外，凋亡是非感染性神经退行性疾病中细胞死亡的常见特征。凋亡程序是一个耗能的，缓慢发展的过程，它分为三个主要步骤。启动，进展和执行。该程序的每个步骤都由许多具有协同或拮抗功能的分子控制，其中半胱氨酸蛋白酶家族（称为胱天蛋白酶）起着主要作用。半胱天冬酶在凋亡过程的所有步骤中的中心位置已导致基于其在靶分子上的优选切割位点的四肽序列的几类抑制药物的发展。最初的化合物类别具有毒性，特异性和血脑屏障穿透性的问题，但即使如此，在神经疾病的动物模型中仍给出了令人鼓舞的临床前结果。已经开发了新一代的抗半胱天冬酶药物，包括已显示出令人满意的药物活性的非基于肽的化合物。另外，临床前的发展包括基于使用胱天蛋白酶天然抑制剂的蛋白质疗法的进步，其具有靶向协同神经保护途径的优势。该策略使用肽载体通过血脑屏障和脑细胞膜携带大分子。尽管临床前数据令人信服，但是这些各种药物家族在患有急性和/或进行性脑损伤的患者中的活性尚未得到证实。

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