Trojanowski John Q, Smith Amos B, Huryn Donna, Lee Virginia M-Y
Expert Opin Pharmacother. 2005 May;6(5):683-6. doi: 10.1517/14656566.6.5.683.
Increasing evidence implicates impairments of axonal transport in mechanisms underlying diverse neurodegenerative disease. This evidence includes discoveries of mutations in genes encoding human motor proteins or proteins involved in stabilising the microtubule (MT) network required for maintenance of axonal transport in familial neurodegenerative disorders, as well as data from in vivo and in vitro model systems. Moreover, in sporadic neurodegenerative disorders such as Alzheimer's disease (AD), pathological alterations of the MT-binding protein tau are linked to impaired axonal transport and brain degeneration. Because MT-stabilising compounds hold promise for counteracting the loss of tau function in AD and sustaining effective axonal transport, we conclude that MT-binding/stabilising drugs show potential therapeutic utility for the treatment of AD and other neurodegenerative disorders characterised by altered MTs and impaired axonal transport.
越来越多的证据表明，轴突运输受损是多种神经退行性疾病潜在机制的一部分。这些证据包括在家族性神经退行性疾病中，编码人类运动蛋白或参与稳定维持轴突运输所需微管（MT）网络的蛋白质的基因突变的发现，以及来自体内和体外模型系统的数据。此外，在散发性神经退行性疾病如阿尔茨海默病（AD）中，MT结合蛋白tau的病理改变与轴突运输受损和脑退化有关。由于MT稳定化合物有望抵消AD中tau功能的丧失并维持有效的轴突运输，我们得出结论，MT结合/稳定药物对治疗AD和其他以MT改变和轴突运输受损为特征的神经退行性疾病具有潜在的治疗效用。
