Gao Yong-Lei, Wang Nan, Sun Fu-Rong, Cao Xi-Peng, Zhang Wei, Yu Jin-Tai
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
Endoscopy Center, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
Ann Transl Med. 2018 May;6(10):175. doi: 10.21037/atm.2018.04.23.
Tau, a microtubule-associated protein, is the main component of the intracellular filamentous inclusions that are involved in neurodegenerative diseases known as tauopathies, including Alzheimer disease (AD), frontotemporal dementia with parkinsonism-17 (FTDP-17), Pick disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Hyperphosphorylated, aggregated tau proteins form the core of neurofibrillary tangles (NFTs), which are shown to be one of the pathological hallmarks of AD. The discovery of mutations in the microtubule-associated protein tau () gene in patients with FTDP-17 also contributes to a better understanding of the dysfunctional tau as a cause of diseases. Although recent substantial progress has been made in the tau pathology of tauopathies, the mechanisms underlying tau-induced neurodegeneration remain unclear. Here, we present an overview of the biochemical properties of tau protein and the pathogenesis underlying tau-induced neurodegenerative diseases. Meanwhile, we will discuss the tau-related biomarkers and ongoing tau-targeted strategies for therapeutic modulation.
tau蛋白是一种微管相关蛋白,是细胞内丝状内含物的主要成分,这些内含物参与了被称为tau蛋白病的神经退行性疾病,包括阿尔茨海默病(AD)、伴有帕金森综合征的额颞叶痴呆-17(FTDP-17)、皮克病(PiD)、进行性核上性麻痹(PSP)和皮质基底节变性(CBD)。高度磷酸化、聚集的tau蛋白形成神经原纤维缠结(NFTs)的核心,而神经原纤维缠结被证明是AD的病理标志之一。FTDP-17患者中微管相关蛋白tau()基因突变的发现也有助于更好地理解功能失调的tau蛋白作为疾病病因的作用。尽管最近在tau蛋白病的tau病理学方面取得了重大进展,但tau蛋白诱导神经退行性变的潜在机制仍不清楚。在此,我们概述了tau蛋白的生化特性以及tau蛋白诱导神经退行性疾病的发病机制。同时,我们将讨论与tau蛋白相关的生物标志物以及正在进行的针对tau蛋白的治疗调节策略。