神经药理学报››2011,Vol. 1››Issue (5): 34-39.
李礼轩1, 李晓辉2
出版日期:
2011-10-26发布日期:
2013-03-24通讯作者:
李晓辉,男,教授,博士,博士生导师;研究方向:抗炎免疫与神经药理学;Tel:+86-023-68752318,Fax:+86-023-68753397,E-mail:lpsh008@yahoo.com.cn作者简介:
李礼轩,男,重庆医科大学2007级临床医学系本科生;E-mail: 1191123502 @qq.com基金资助:
国家自然科学基金(No.30973523)
LI Li-xuan1, LI Xiao-hui2
Online:
2011-10-26Published:
2013-03-24Contact:
李晓辉,男,教授,博士,博士生导师;研究方向:抗炎免疫与神经药理学;Tel:+86-023-68752318,Fax:+86-023-68753397,E-mail:lpsh008@yahoo.com.cnAbout author:
李礼轩,男,重庆医科大学2007级临床医学系本科生;E-mail: 1191123502 @qq.comSupported by:
国家自然科学基金(No.30973523)
摘要:Tau蛋白是神经细胞特有的微管相关蛋白,其基本功能是促进微管蛋白组装成微管,维持正常神经轴突运输及微管稳定性。既往基于尸检发现脑部神经纤维缠结(neurofibrillary tangles,NFTs) 与神经元死亡、细胞形态异常及凋亡之间呈良好的平行关系,因而NFTs被认为是引起神经退行性Tau蛋白病的重要原因,并认为与Tau蛋白的过磷酸化有关;但新近发现单纯Tau蛋白磷酸化并不足以形成NFTs,还必须有其他诸如糖基化、脯氨酸异构化、泛素化等翻译后修饰机制的协同,其他如Tau蛋白基因突变、自噬的抑制等也与NFTs形成有关。尤其是最近采用转基因活体动物和多光子影像技术的研究显示,NFTs可能只是疾病晚期的临床表现,而可溶性的Tau蛋白才是启动下游病理反应的关键因素。更为引人注目的是,抑制Tau蛋白还可以阻止Aβ引起的神经细胞凋亡、减轻记忆损害,换言之即Aβ的毒性是Tau蛋白依赖性的。随着近期对Tau蛋白异常介导神经退行性Tau蛋白病及其机制的新认识以及以Aβ为靶点的药物研发宣告失败,人们愈来愈重视以Tau 为靶点的药物开发。
中图分类号:
李礼轩, 李晓辉. Tau蛋白异常导致阿尔茨海默病等神经退行性Tau蛋白病的机制与研究进展[J]. 神经药理学报, 2011, 1(5): 34-39.
LI Li-xuan, LI Xiao-hui. The Mechanisms and Research Progress of Tau Abnormality Leading to AD Related Neurodegenerative Taupathies[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(5): 34-39.
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