Tau in Alzheimer's Disease: Pathological Alterations and an Attractive Therapeutic Target
Tau in Alzheimer's Disease: Pathological Alterations and an Attractive Therapeutic Target
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DOI：
10.1007/s11596-020-2282-1
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发表时间：
2020-12-01
影响因子：
2.4
通讯作者：
Liu, Fei
中科院分区：
文献类型：
--
作者：
Gu, Jian-lan;Liu, Fei
阿尔茨海默病（AD）是一种年龄相关的神经退行性疾病，具有两个主要特征：由淀粉样蛋白-β（A β）制成的细胞外淀粉样蛋白斑块和异常过度磷酸化的tau的细胞内神经元缠结（NFT）。NFT的数量与AD患者痴呆的严重程度呈正相关。然而，迄今为止，仍然没有有效的治疗和预防AD的疗法。在过去的几十年里，对AD发病机制的深入了解已经确定了产生特异性治疗的新策略。几项研究表明，朊病毒样接种和tau病理在大脑中的传播可能是AD的关键驱动因素。Tau蛋白由于其在多种神经退行性疾病中的重要病理作用而被认为是开发治疗干预的有希望的候选靶标。异常的tau蛋白过度磷酸化起着有害的病理作用，最终导致神经变性。本文就tau蛋白在AD发病机制中的研究进展作一综述，并简要讨论基于tau蛋白的治疗策略。
Alzheimer's disease (AD) is an age-related neurodegenerative disease with two major hallmarks: extracellular amyloid plaques made of amyloid-beta (A beta) and intracellular neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau. The number of NFTs correlates positively with the severity of dementia in AD patients. However, there is still no efficient therapy available for AD treatment and prevention so far. A deeper understanding of AD pathogenesis has identified novel strategies for the generation of specific therapies over the past few decades. Several studies have suggested that the prion-like seeding and spreading of tau pathology in the brain may be a key driver of AD. Tau protein is considered as a promising candidate target for the development of therapeutic interventions due to its considerable pathological role in a variety of neurodegenerative disorders. Abnormal tau hyperphosphorylation plays a detrimental pathological role, eventually leading to neurodegeneration. In the present review, we describe the recent research progresses in the pathological mechanisms of tau protein in AD and briefly discuss tau-based therapeutic strategies.