摘要
目的:阿尔茨海默病具有神经原纤维缠结和tau蛋白的异常过度磷酸化两大病理特征,可导致神经细胞骨架异常并与神经元死亡有关。近来的一些理论提出了糖原合酶激酶3参与上述两大病理特征的形成,从而在阿尔茨海默病发病中具有重要作用的相关假设。资料来源:应用网络Medline检索1986/2002关于阿尔茨海默病的相关文献,检索词:阿尔茨海默病(Alzheimerdisease),糖原合酶激酶3(glycogensynthasekinase-3),tau蛋白。资料选择:选择关于糖原合酶激酶3与阿尔茨海默病发病关系的相关文献,以非随机研究原著和没有对照组的研究为纳入标准,未排除非盲法研究,排除重复性文献和综述性文献。资料提炼:在66篇文献中,内容呈不同程度重复的有13篇,给予删除;对53篇文献进行分类整理分析,其中33篇选用为参考文献。资料综合:糖原合酶激酶3β能在大多数阿尔茨海默病相关位点磷酸化tau蛋白,本身的活性又同时受到蛋白激酶与蛋白磷酸酯酶的双重调节;糖原合酶激酶3β在引起tau蛋白异常过度磷酸化的同时,在细胞水平还引起神经元的凋亡;整体实验也显示糖原合酶激酶3β可能导致轴突转运障碍。结论:糖原合酶激酶3β不但直接导致tau蛋白的异常过度磷酸化,使组织内出现类似于阿尔茨海默病患者脑内神经原纤维缠结样细胞。
OBJECTIVE:Alzheimer disease has two pathological characteristics of neurofibrillary tangles and abnormally hyperphosphorylated tau protein,which can lead to the abnormality of neural cytoskeleton and are associated with the neuronal death.Recently, some theories suggest relevant assumption that glycogen synthase kinase 3 participates in the formation of the above two pathological characteristics,so that it plays an important role in the attack of Alzheimer disease.DATA SOURCES:An online search of Medline was undertaken to identify articles related to Alzheimer disease published between 1986 and 2002 by using the keywords of “ Alzheimer disease,glycogen synthase kinase 3,tau protein'.STUDY SELECTION:Articles about the association between glycogen synthase kinase 3 and the attack of Alzheimer disease were selected.The inclusion criteria was non randomized original work,study without control group;Non blinded studies were not excluded,and repetitive articles and reviews were deleted. DATA EXTRACTION:Among the 66 articles,13 were deleted for repetitive content to different degree,and the other 53 were classified and analyzed,33 of them served as references.DATA SYNTHESIS:Glycogen synthase kinase 3 beta,whose activity was double regulated by protein kinase and protein phosphatase,could phosphorylate tau protein at most sites related to Alzheimer disease,at the same time it also led to the apoptosis of neuron on cellular level.The integral experiment also showed that glycogen synthase kinase 3 beta could cause the disorder of axonal transport. CONCLUSION:Glycogen synthase kinase 3 beta cannot only lead to the abnormal hyperphosphorylation of tau protein,which can form cells like neurofibrillary tangle similar to those in the brain of patients with Alzheimer disease in tissue,but also play an important role in the apoptosis of neurons.It has many substrates of action and complex regulative methods,so it is the key molecule for the attack of Alzheimer disease,and also possibly the meeting point for various factors that can result in the injury of neurons.
出处
《中国临床康复》
CSCD
北大核心
2005年第17期142-144,共3页
Chinese Journal of Clinical Rehabilitation
