Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies.
Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies.
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DOI：
10.1021/jm301079z
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发表时间：
2012-11-08
影响因子：
7.3
通讯作者：
Smith, Amos B., III
中科院分区：
文献类型：
--
作者：
Ballatore, Carlo;Brunden, Kurt R.;Huryn, Donna M.;Trojanowski, John Q.;Lee, Virginia M. -Y.;Smith, Amos B., III
微管（MT）相关蛋白 tau 在神经元轴突中高表达，是一种内源性 MT 稳定剂，在轴突运输中发挥重要作用。 tau 蛋白错误折叠、过度磷酸化和隔离成不溶性聚集体导致 MT 稳定 tau 功能的丧失，导致轴突运输缺陷，从而产生神经病理学后果。多项体外和临床前体内研究表明，MT 稳定药物可用于补偿 tau 功能的丧失并维持/恢复有效的轴突运输。这些发现表明，MT 稳定化合物在治疗阿尔茨海默病和相关 tau蛋白病方面具有广阔的前景。本文概述了证明 MT 稳定药物在神经退行性 tau蛋白病中的治疗潜力的关键发现，并对不同类别的 MT 稳定化合物进行了概述。
The microtubule (MT)-associated protein tau, which is highly expressed in the axons of neurons, is an endogenous MT-stabilizing agent that plays an important role in the axonal transport. Loss of MT-stabilizing tau function, caused by misfolding, hyperphosphorylation and sequestration of tau into insoluble aggregates, leads to axonal transport deficits with neuropathological consequences. Several in vitro and preclinical in vivo studies have shown that MT-stabilizing drugs can be utilized to compensate for the loss of tau function and to maintain/restore an effective axonal transport. These findings indicate that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeutic potential of MT-stabilizing drugs in the context of neurodegenerative tauopathies, as well as an overview of the different classes of MT-stabilizing compounds.
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