Department of Pharmacology, China Pharmaceutical University, Nanjing, People's Republic of China.
Department of Pharmacology, China Pharmaceutical University, Nanjing, People's Republic of China.
Neurobiol Aging. 2021 Mar;99:79-85. doi: 10.1016/j.neurobiolaging.2020.11.015. Epub 2020 Dec 8.
Accumulation of phosphorylated tau (p-tau) has long been an underappreciated hallmark of Alzheimer's disease. Tau is one of the major components of microtubule networks in neurons, and its abnormal phosphorylation and aggregation are closely related to the impairment of axonal transport. Abnormalities in axonal transport can impede autophagy in neurons, interrupting the autophagic clearance of amyloid beta. The ubiquitin proteasome system (UPS) maintains intracellular proteostasis by degrading abnormal or redundant proteins. Ever-mounting evidence suggests that UPS deficits contribute to p-tau accumulation. And targeting UPS attenuates tau pathology. This review endeavors to exam the potential role of UPS in p-tau aggregation, and how pathogenic tau may inflict other abnormalities such as amyloid beta accumulation in Alzheimer's disease.
磷酸化tau（p-tau）的积累一直以来都是阿尔茨海默病被低估的一个标志性特征。tau 是神经元微管网络的主要成分之一，其异常磷酸化和聚集与轴突运输的损伤密切相关。轴突运输异常会阻碍神经元中的自噬，从而中断淀粉样β的自噬清除。泛素蛋白酶体系统（UPS）通过降解异常或多余的蛋白质来维持细胞内蛋白质的稳态。越来越多的证据表明，UPS 的缺陷会导致 p-tau 的积累。而靶向 UPS 可以减轻 tau 病理。这篇综述旨在探讨 UPS 在 p-tau 聚集中的潜在作用，以及致病性 tau 如何在阿尔茨海默病中引发其他异常，如淀粉样β的积累。
