Review Article

阿尔茨海默病潜在酶靶点的综合评价

卷 20, 期 3, 2019

页: [316 - 339] 页: 24

弟呕挨: 10.2174/1389450119666180820104723

价格: $65

摘要

阿尔茨海默氏症是脑细胞退化的原因,被称为进行性神经退行性疾病,其病因似乎多种多样,主要强调淀粉样级联和过度磷酸化的tau级联假说,这些假说与被称为酶的大分子(如-&-分泌酶、大肠杆菌、转葡萄糖)直接相关。泰米尔酶、糖原合成酶激酶(GSK-3)、细胞周期蛋白依赖激酶(CDK-5)、微管亲和力调节激酶(mark)。上述酶的催化活性是由认知缺陷、记忆障碍、突触功能障碍和丧失以及最终神经元死亡引起的。然而,其他一些酶在大脑中的活动和水平降低到正常水平时也会导致这些功能异常事件,如-分泌酶、蛋白激酶C、磷酸酶等;代谢成神经递质、单胺氧化酶(MAO)、儿茶酚-O-甲基转移酶(COMT)等酶。或者,当这些酶在大脑中的活动和水平降低到正常水平时,这些异常也会发生。磷酸二酯酶(phosphodiesterase)等其他机制的作用降低了大脑核苷酸(cgmp和cAMP)水平,磷脂酶A2:pla2与活性氧(ROS)的产生等有关。在治疗方面,通过针对不同的酶来开发治疗阿尔茨海默病的新疗法,正在进行一些重要的临床试验。如-分泌酶抑制剂、GSK-3、MAO、磷酸二酯酶、PLA2、胆碱酯酶等,以及-分泌酶活性调节剂和蛋白激酶C、sirtuins的激活剂等。近几十年来,人们越来越关注研究结果,寻找阿尔茨海默病新的假定和新的酶靶点。本文综述了阿尔茨海默病的功能。几乎所有阿尔茨海默病相关酶的作用、病理作用和价值,这些酶涉及治疗阿尔茨海默病的策略和预防方法。

关键词: 老年痴呆症,记忆和认知,酶,酶靶,治疗学,临床试验。

图形摘要
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