阿尔茨海默病及相关疾病中tau蛋白介导的神经退行性变。

Tau-mediated neurodegeneration in Alzheimer's disease and related disorders.

作者信息

Ballatore Carlo, Lee Virginia M-Y, Trojanowski John Q

机构信息

Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104-4283, USA.

出版信息

Nat Rev Neurosci. 2007 Sep;8(9):663-72. doi: 10.1038/nrn2194.

DOI:10.1038/nrn2194

PMID:17684513

Abstract

Advances in our understanding of the mechanisms of tau-mediated neurodegeneration in Alzheimer's disease (AD) and related tauopathies, which are characterized by prominent CNS accumulations of fibrillar tau inclusions, are rapidly moving this previously underexplored disease pathway to centre stage for disease-modifying drug discovery efforts. However, controversies abound concerning whether or not the deleterious effects of tau pathologies result from toxic gains-of-function by pathological tau or from critical losses of normal tau function in the disease state. This Review summarizes the most recent advances in our knowledge of the mechanisms of tau-mediated neurodegeneration to forge an integrated concept of those tau-linked disease processes that drive the onset and progression of AD and related tauopathies.

摘要

在我们对阿尔茨海默病（AD）及相关tau蛋白病中tau介导的神经退行性变机制的理解方面取得了进展，这些疾病的特征是中枢神经系统中显著积累纤维状tau蛋白包涵体，这正迅速将这条此前未被充分探索的疾病途径推向疾病修饰药物研发努力的核心位置。然而，关于tau蛋白病变的有害影响是源于病理性tau蛋白的毒性功能获得还是疾病状态下正常tau蛋白功能的关键丧失，存在诸多争议。本综述总结了我们在tau介导的神经退行性变机制知识方面的最新进展，以形成一个关于那些驱动AD及相关tau蛋白病发病和进展的tau相关疾病过程的综合概念。