阿尔茨海默病中P38MAPK信号通路研究进展.doc

阿尔茨海默病中p38MAPK信号通路的研究进展 【摘要】随着人类步入老龄化社会, 阿尔茨海默病(Alzheimers disease, AD)的发病率不断增加, 但其发病机制仍不明确。近年来研究发现p38MAPK信号通路既参与了AD中Aβ沉积所致的小胶质细胞和星形胶质细胞的活化，又与Tau蛋白的异常磷酸化密切相关。本文将对以上内容进行综述。 【关键词】p38MAPK信号通路；阿尔茨海默病；β-淀粉样肽；tau蛋白 Progress of p38MAPK signal way in Alzheimer’s Disease Wang Di; Zhou Yan (clinical medicine of seven years in Grade 09,Capital Medical University ; Basic Medical College, Capital Medical 【ABSTRACT】In modern aging society, the incidence of Alzheimers disease (AD) has been increasing significantly. However, the pathogenesis of AD has not ever been elucidated. Recent study reported that the p38MAPK signal way is significantly related to both the activation of microglia as well as astrocytes and phosphorylation of Tau protein. Here we provide a review on the mechanism of p38MAPK talked above. 【KEY WORDS】p38MAPK; Alzheimers disease; Amyloid-beta peptide; Tau protein 阿尔茨海默病(Alzheimer’s Disease, AD)是一种常见于老年人的中枢神经系统退行性变疾病,以进行性认知功能障碍、精神行为异常及生活能力减退等为主要表现,是痴呆病中最常见的类型。其特征性病理学改变为脑神经细胞外出现淀粉样蛋白(Amyloid-beta peptide,Aβ)聚集形成的老年斑,脑神经细胞内tau蛋白异常聚集形成的神经原纤维缠结,脑皮质细胞有不同程度的减少以及星形胶质细胞的增生及肥大, 并且脑内有大量的Aβ的沉积。其中Aβ肽可引起炎症反应而致神经元丧失和认知功能障碍[]Tyler A. Kokjohn, Gregory D. Van Vickle, Chera L. Maarouf, []Tyler A. Kokjohn, Gregory D. Van Vickle, Chera L. Maarouf, et al. Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets[J]. Biochimica et Biophysica Acta, 2011, 1812: 1508–1514. AD患者尸检发现脑内p38活性升高[]Swatton JE, Sellers LA, Faull RL, et al. Increased MAP kinase activity in Alzheimers and Down syndrome but not in schizophrenia human brain[J]．Eur J Neurosci,2004,19: 2711-2719． ，提示AD的病理变化与 []Swatton JE, Sellers LA, Faull RL, et al. Increased MAP kinase activity in Alzheimers and Down syndrome but not in schizophrenia human brain[J]．Eur J Neurosci,2004,19: 2711-2719． 1 p38MAPK信号通路 1.1 p38MAPK信号通路的组成 p38MAPK是哺乳动物应激与炎症激活的丝裂原活化蛋白激酶（MAPK）家族的重要组成成分。p38 MAPK通过磷酸化三级酶促级联反应把细胞外信号向细胞内传递，其中包括要三个关键激酶: MAPK、MAPKK、MAPKKK