Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, 94158, USA.
Genes Immun. 2020 Nov;21(5):288-300. doi: 10.1038/s41435-020-00113-5. Epub 2020 Oct 3.
Tau is an evolutionary conserved protein that promotes the assembly and stabilization of microtubules in neuronal axons. Complex patterns of posttranslational modifications (PTMs) dynamically regulate tau biochemical properties and consequently its functions. An imbalance in tau PTMs has been connected with a broad spectrum of neurodegenerative conditions which are collectively known as tauopathies and include Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) among others. The hallmark of these neurological disorders is the presence in the brain of fibrillary tangles constituted of misfolded species of hyper-phosphorylated tau. The pathological events leading to tau aggregation are still largely unknown but increasing evidence suggests that neuroinflammation plays a critical role in tangle formation. Moreover, tau aggregation itself could enhance inflammation through feed-forward mechanisms, amplifying the initial neurotoxic insults. Protective effects of tau against neuroinflammation have been also documented, adding another layer of complexity to this phenomenon. Here, we will review the current knowledge on tau regulation and function in health and disease. In particular, we will address its emerging role in connecting neurodegenerative and neuroinflammatory processes.
tau 是一种进化上保守的蛋白质，它能促进神经元轴突中微管的组装和稳定。翻译后修饰（PTMs）的复杂模式能动态调节 tau 的生化特性，从而影响其功能。tau PTM 的失衡与广泛的神经退行性疾病有关，这些疾病统称为 tau 病，包括阿尔茨海默病（AD）、进行性核上性麻痹（PSP）和皮质基底节变性（CBD）等。这些神经紊乱的标志是大脑中存在由异常折叠的过度磷酸化 tau 组成的纤维缠结。导致 tau 聚集的病理事件在很大程度上仍然未知，但越来越多的证据表明神经炎症在缠结形成中起着关键作用。此外，tau 聚集本身可以通过正反馈机制增强炎症，放大最初的神经毒性损伤。tau 对神经炎症的保护作用也有记录，这为这一现象增加了另一层复杂性。在这里，我们将回顾 tau 在健康和疾病中的调节和功能的现有知识。特别是，我们将讨论它在连接神经退行性和神经炎症过程中的新作用。
