Advances in tau-based drug discovery.
Advances in tau-based drug discovery.
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DOI：
10.1517/17460441.2011.586690
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发表时间：
2011-08-01
影响因子：
6.3
通讯作者：
Hanger DP
中科院分区：
文献类型：
--
作者：
Noble W;Pooler AM;Hanger DP
Tau蛋白病，包括阿尔茨海默病（AD）和一些额颞痴呆，是以包含Tau蛋白的病理学病变为特征的神经退行性疾病。目前对这些病症的疾病修饰疗法存在显著且迫切的未满足需求，并且最近注意力已转向tau作为潜在的干预靶点。越来越多的证据强调了与tau介导的神经变性相关的途径是药物开发的重要靶点。在这里，作者回顾了最近发表的这一领域的论文，并总结了在减少tau相关神经退行性变方面表现出有效性的遗传和药理学方法。这些包括使用试剂来防止异常tau加工和增加tau清除，靶向免疫系统的疗法，以及操纵tau前mRNA以修饰tau同种型表达。目前正在临床试验中评估几种基于小分子tau的治疗方法，其结果令人期待。目前的证据表明，靶向tau的疗法可能至少部分地形成有效和安全治疗阿尔茨海默病和tau沉积明显的相关神经退行性疾病的基础。
Tauopathies, including Alzheimer’s disease (AD) and some frontotemporal dementias, are neurodegenerative diseases characterised by pathological lesions comprised of tau protein. There is currently a significant and urgent unmet need for disease-modifying therapies for these conditions and recently attention has turned to tau as a potential target for intervention. Increasing evidence has highlighted pathways associated with tau-mediated neurodegeneration as important targets for drug development. Here, the authors review recently published papers in this area and summarise the genetic and pharmacological approaches that have shown efficacy in reducing tau-associated neurodegeneration. These include the use of agents to prevent abnormal tau processing and increase tau clearance, therapies targeting the immune system, and the manipulation of tau pre-mRNA to modify tau isoform expression. Several small molecule tau-based treatments are currently being assessed in clinical trials, the outcomes of which are eagerly awaited. Current evidence suggests that therapies targeting tau are likely, at least in part, to form the basis of an effective and safe treatment for Alzheimer’s disease and related neurodegenerative disorders in which tau deposition is evident.
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影响因子：
7.3
作者：
Chang E;Congdon EE;Honson NS;Duff KE;Kuret J
通讯作者：
Kuret J
影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
DOI：
10.1016/j.bbrc.2007.03.056
发表时间：
2007-06-22
影响因子：
3.1
作者：
Crowe, Alex;Ballatore, Carlo;Lee, Virginia M. -Y.
通讯作者：
Lee, Virginia M. -Y.
影响因子：
--
作者：
Coghlan, MP;Culbert, AA;Holder, JC
通讯作者：
Holder, JC
影响因子：
5.3
作者：
Boimel, Moran;Grigoriadis, Nikolaos;Rosenmann, Hanna
通讯作者：
Rosenmann, Hanna