Tau protein is involved in various cellular processes, including having a canonical role in binding and stabilization of microtubules in neurons. Tauopathies are neurodegenerative diseases marked by the abnormal accumulation of tau protein aggregates in neurons, as seen, for example, in conditions such as frontotemporal dementia and Alzheimer disease. Mutations in tau coding regions or that disrupt tau mRNA splicing, tau post-translational modifications and cellular stress factors (such as oxidative stress and inflammation) increase the tendency of tau to aggregate and interfere with its clearance. Pathological tau is strongly implicated in the progression of neurodegenerative diseases, and the propagation of tau aggregates is associated with disease severity. Recent technological advancements, including cryo-electron microscopy and disease models derived from human induced pluripotent stem cells, have increased our understanding of tau-related pathology in neurodegenerative conditions. Substantial progress has been made in deciphering tau aggregate structures and the molecular mechanisms that underlie protein aggregation and toxicity. In this Review, we discuss recent insights into the diverse cellular functions of tau and the pathology of tau inclusions and explore the potential for therapeutic interventions.

Tau 蛋白参与各种细胞过程，包括在神经元微管的结合和稳定中起经典作用。tau 蛋白病是神经退行性疾病，其特征是 tau 蛋白聚集体在神经元中异常积累，例如，在额颞叶痴呆和阿尔茨海默病等情况下可见。tau 编码区的突变或破坏 tau mRNA 剪接、tau 翻译后修饰和细胞应激因子（如氧化应激和炎症）的突变会增加 tau 聚集并干扰其清除的趋势。病理性 tau 与神经退行性疾病的进展密切相关，tau 聚集体的传播与疾病严重程度相关。最近的技术进步，包括冷冻电子显微镜和源自人类诱导多能干细胞的疾病模型，增加了我们对神经退行性疾病中 tau 相关病理学的理解。在破译 tau 聚集体结构以及蛋白质聚集和毒性的分子机制方面已经取得了重大进展。在这篇综述中，我们讨论了对 tau 的不同细胞功能和 tau 包涵体病理学的最新见解，并探讨了治疗干预的潜力。