A current view on Tau protein phosphorylation in Alzheimer's disease

作者：Susanne Wegmann, Jacek Biernat, Eckhard Mandelkow� · 发表于：Current Opinion in Neurobiology · 年份：2021 · DOI：10.1016/j.conb.2021.03.003 · 被引用次数：466 · 研究领域：Alzheimer's disease research and treatments、Cholinesterase and Neurodegenerative Diseases、Neuroscience and Neuropharmacology Research

The functions of the neuronal microtubule-associated protein Tau in the central nervous system are regulated by manifold posttranslational modifications at more than 50 sites. Tau in healthy neurons carries multiple phosphate groups, mostly in its microtubule assembly domain. Elevated phosphorylation and aggregation of Tau are widely considered pathological hallmarks in Alzheimer's disease (AD) and other tauopathies, triggering the quest for Tau posttranslational modifications in the disease context. However, the phosphorylation patterns of physiological and pathological Tau are surprisingly similar and heterogenous, making it difficult to identify specific modifications as therapeutic targets and biomarkers for AD. We present a concise summary of - and view on - important previous and recent advances in Tau phosphorylation analysis in the context of AD.