Considerations for future tau-targeted therapeutics: can they deliver?
Considerations for future tau-targeted therapeutics: can they deliver?
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未来 tau 靶向疗法的考虑因素：它们能发挥作用吗？
DOI：
10.1080/17460441.2020.1685977
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发表时间：
2020
影响因子：
6.3
通讯作者：
Noble W
中科院分区：
文献类型：
--
作者：
Noble W
阿尔茨海默氏病(AD)是老年人痴呆症最常见的原因，也是导致死亡的主要原因。β-淀粉样蛋白和tau蛋白在AD脑内的进行性积聚和扩散与突触丢失和神经变性有关。最近的证据表明，虽然淀粉样前体蛋白加工的改变和β-淀粉样蛋白的积聚可能会引发AD，但异常的tau是执行者。tau通常是一种高度可溶性的细胞质蛋白，它与微管动态相互作用，稳定细胞骨架，调节轴突运输。当被修饰时，包括过度磷酸化、切割和聚集，tau在AD和相关的tauopathy，如进行性核上性麻痹(PSP)和某些形式的额颞叶痴呆(FTD)中积累为神经纤维性病理[1]。病理性tau物种表现为相互作用和定位改变，生理功能丧失，Pron样传播特征，通过病变的大脑促进tau病理的进行性出现，以及毒性功能的获得。例如，病理性tau从胞浆到突触的错误定位导致突触前功能丧失，促进突触后兴奋性毒性，并与AD痴呆密切相关[1，2]。在这里，我们讨论tau靶向治疗的现状。
AlzheimerLs disease (AD) is the most common cause of dementia in the elderly and a leading cause of death. The progressive accumulation and spread of β-amyloid and tau in AD brain are linked with synaptic loss and neurodegeneration. Recent evidence indicates that while alterations in amyloid precursor protein processing and β-amyloid accumulation likely trigger AD, abnormal tau acts as the executioner.Tau is normally a highly soluble cytoplasmic protein that dynamically interacts with microtubules to stabilize the cytoskeleton and regulate axonal transport. When modified, including by hyperphosphorylation, cleavage and aggregation, tau accumulates as neurofibrillary pathology in AD and related tauopathies such as progressive supranuclear palsy (PSP) and some forms of frontotemporal dementia (FTD)[1]. Pathological tau species show altered interactions and localization, loss of physiological function, prion-like spread characteristics that promote the progressive appearance of tau pathology through diseased brain, and gain of toxic functions. For example, the mislocalization of pathological tau from the cytoplasm to synapses causes loss of presynaptic function, promotes post-synaptic excitotoxicity, and is closely associated with dementia in AD [1, 2]. Here, we discuss the current state of tau-targeting therapies.
IONIS-MAPTRx（一种降低 Tau 的反义寡核苷酸）在阿尔茨海默病患者中的首次人体研究设计 (S2.006)
影响因子：
9.9
作者：
L. Mignon;H. Kordasiewicz;R. Lane;Anne V Smith;T. Miller;P. Narayanan;E. Swayze;D. Norris;B. Fitzsimmons;F. Bennett
通讯作者：
F. Bennett
影响因子：
14.5
作者：
Perez-Nievas, Beatriz G.;Stein, Thor D.;Gomez-Isla, Teresa
通讯作者：
Gomez-Isla, Teresa