生命基因在衰老和阿尔茨海默病中的作用及其药理学研究进展.pdfVIP

药学学报 Acta Pharmaceutica Sinica 2009, 44 (8): 825−832 ·825 · ·综述· 生命基因在衰老和阿尔茨海默病中的作用及其药理学研究进展 * 侯 艳 , 鲍秀琦, 刘耕陶 ( 中国医学科学院、北京协和医学院药物研究所, 北京 100050) 摘要: 衰老的自由基假说强调了衰老过程中自由基的积累导致细胞损伤。阿尔茨海默病是多发于老年人的 以认知和记忆功能障碍为特点的神经退行性疾病。衰老是阿尔茨海默病的关键危险因素。大量证据表明, 机体 自由基生成和清除平衡的破坏是促进衰老和神经退行性改变的主要原因。脑组织通过诱导一系列基因的表达对 抗氧化应激, 这些基因被称作生命基因。生命基因的表达产物主要包括热休克蛋白家族、血红素加氧酶系统和 硫氧还蛋白系统, 他们构成了机体内源性的防御系统。本文综述了生命基因在衰老和阿尔茨海默病脑组织中的 表达和功能, 以及相关药理学研究。 关键词: 衰老; 阿尔茨海默病; 热休克蛋白; 血红素加氧酶; 硫氧还蛋白 中图分类号: R963 文献标识码: A 文章编号: 0513-4870 (2009) 08-0825-08 The role of vitagene in aging and Alzheimer’s disease and relevant advances of pharmacological study * HOU Yan , BAO Xiu-qi, LIU Geng-tao (Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China) Abstract: Free radical hypothesis of aging emphasized that the age-related accumulation of free radicals results in cell injury. Alzheimer’s disease (AD) is the most common form of neurodegenerative disease charac- terized by impaired cognition and memory of the elderly. Aging is a key risk factor in AD. Substantial evidence suggests that imbalance between free radical formation and clearance promotes AD pathogenesis. The brain overcomes oxidative stress by inducing expression of a set of genes called vitagenes. The protein products of vitagenes include heat shock proteins, heme oxygenases and thioredoxin systems, which serve as endogenous lifeguard of cells. This pap