Rankin Carolyn A, Gamblin T Chris
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
J Alzheimers Dis. 2008 Aug;14(4):411-6. doi: 10.3233/jad-2008-14408.
Abnormally phosphorylated and aggregated tau protein is the primary component of pathological structures that are closely associated with neurodegeneration in Alzheimer's disease, Pick disease, corticobasal degeneration, progressive supranuclear palsy and many other neurodegenerative tauopathies, leading to the hypothesis that these structures are toxic mediators of disease progression. Results from animal models designed to test this hypothesis have yielded evidence that can suggest either a pathogenic, beneficial, or incidental role for tau aggregation. This review summarizes the differences in construction of recent model systems and assay methods that examine tau pathology and toxicity. We have found that the expression levels of tau and the modifications of tau used to enhance its aggregation have a large impact on the results. It is clear from the data that tau aggregation is toxic, but it is less clear which form of tau aggregate is the toxic species.
异常磷酸化和聚集的tau蛋白是与阿尔茨海默病、皮克病、皮质基底节变性、进行性核上性麻痹以及许多其他神经退行性tau蛋白病中的神经退行性变密切相关的病理结构的主要成分，这导致了一种假说，即这些结构是疾病进展的毒性介质。旨在验证这一假说的动物模型结果提供了证据，表明tau聚集可能具有致病、有益或偶然的作用。本综述总结了最近用于研究tau病理学和毒性的模型系统构建和检测方法的差异。我们发现tau的表达水平以及用于增强其聚集的tau修饰对结果有很大影响。从数据中可以清楚地看出tau聚集是有毒的，但尚不清楚哪种形式的tau聚集体是有毒物种。
