Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing city, 100091, China.
Jining Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shandong province, 272000, China.
J Neurol. 2022 Mar;269(3):1164-1181. doi: 10.1007/s00415-021-10573-y. Epub 2021 Apr 28.
Tubulin-associated unit (tau) is an important microtubule-associated protein. The abnormal intracellular aggregation of tau has been strongly associated with Alzheimer's disease (AD). Accumulating evidence has conclusively demonstrated that tau is present in the cytoplasm of neurons and is also actively released into the extracellular space. However, the types of tau species that are released are unclear, as is the mechanism of their release by donor neurons and subsequent uptake by recipient neurons in AD. Understanding the underlying mechanisms of abnormal tau cell-to-cell transmission can provide novel insights into the etiology and pathogenesis of AD and can help identify new targets for the development of AD therapies focused on counteracting neurodegeneration or even preventing it. From this perspective, the present review focuses on recent advances in understanding the mechanisms regulating the levels of extracellular tau and discusses the role of such mechanisms in the propagation of tau-associated pathology.
微管相关蛋白（tau）是一种重要的微管相关蛋白。tau 的细胞内异常聚集与阿尔茨海默病（AD）密切相关。越来越多的证据确凿地表明，tau 存在于神经元的细胞质中，并且也被积极地释放到细胞外空间。然而，释放的 tau 物种的类型尚不清楚，以及供体细胞神经元释放它们的机制和 AD 中受体细胞的摄取机制尚不清楚。了解异常 tau 细胞间传递的潜在机制可以为 AD 的病因和发病机制提供新的见解，并有助于确定针对对抗神经退行性变甚至预防神经退行性变的 AD 治疗的新靶点。从这个角度来看，本综述重点介绍了理解调节细胞外 tau 水平的机制的最新进展，并讨论了这些机制在 tau 相关病理传播中的作用。
