Phosphorylated tau targeted small-molecule PROTACs for the treatment of Alzheimer's disease and tauopathies.
Phosphorylated tau targeted small-molecule PROTACs for the treatment of Alzheimer's disease and tauopathies.
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DOI：
10.1016/j.bbadis.2021.166162
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发表时间：
2021-08-01
期刊：
影响因子：
--
通讯作者：
Reddy PH
中科院分区：
文献类型：
--
作者：
Jangampalli Adi P;Reddy PH
Tau是一种微管稳定蛋白，在神经元轴突微管的形成中起重要作用。磷酸化tau蛋白（p-Tau）由于与突触损伤和神经元功能障碍有关而成为阿尔茨海默病（AD）的潜在治疗靶点，在AD领域受到了广泛关注。越来越多的证据表明，淀粉样蛋白β（Aβ）靶向临床试验不断失败;因此，重要的是要考虑替代治疗策略，如针对AD和其他tau蛋白病的p-tau-PROTAC靶向小分子。本文描述了AD中健康和病理状态下tau蛋白的生物学、结构和功能特征。它还解释了来自研究的数据，这些研究已经确定了p-tau参与AD的神经元损伤以及突触和认知功能。目前的文章还涵盖了几个方面，包括小分子抑制剂，以及开发p-tau-PROTAC靶向药物分子来治疗AD和其他tau蛋白病患者。
Tau is a microtubule-stabilizing protein that plays an important role in the formation of axonal microtubules in neurons. Phosphorylated tau (p-Tau) has received great attention in the field of Alzheimer’s disease (AD) as a potential therapeutic target due to its involvement with synaptic damage and neuronal dysfunction. Mounting evidence suggests that amyloid beta (Aβ)-targeted clinical trials continuously failed; therefore, it is important to consider alternative therapeutic strategies such as p-tau-PROTACs targeted small molecules for AD and other tauopathies. The present article describes the characteristics of tau biology, structure, and function in both healthy and pathological states in AD. It also explains data from studies that have identified the involvement of p-tau in neuronal damage and synaptic and cognitive functions in AD. Current article also covers several aspects, including small molecule inhibitors, and the development of p-tau-PROTACs targeted drug molecules to treat patients with AD and other tauopathies.
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影响因子：
16.2
作者：
Hoover, Brian R.;Reed, Miranda N.;Su, Jianjun;Penrod, Rachel D.;Kotilinek, Linda A.;Grant, Marianne K.;Pitstick, Rose;Carlson, George A.;Lanier, Lorene M.;Yuan, Li-Lian;Ashe, Karen H.;Liao, Dezhi
通讯作者：
Liao, Dezhi
影响因子：
4.8
作者：
Avila J;Jiménez JS;Sayas CL;Bolós M;Zabala JC;Rivas G;Hernández F
通讯作者：
Hernández F
影响因子：
7
作者：
Hosokawa, Tomohisa;Saito, Taro;Hisanaga, Shin-ichi
通讯作者：
Hisanaga, Shin-ichi
DOI：
10.3233/jad-160076
发表时间：
2016-04-15
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Hensley K;Kursula P
通讯作者：
Kursula P
影响因子：
5.6
作者：
Drummond, Michael L.;Henry, Andrew;Williams, Christopher, I
通讯作者：
Williams, Christopher, I