Gladstone Institute of Neurological Disease, San Francisco, California, United States of America.
PLoS One. 2011;6(12):e29257. doi: 10.1371/journal.pone.0029257. Epub 2011 Dec 19.
Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or transgene-mediated neuronal expression of human wildtype α-synuclein. Both models were evaluated on Tau(+/+), Tau(+/-) and Tau(-/-) backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum. Similarly, tau reduction did not prevent motor deficits in α-synuclein transgenic mice. Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition.
许多神经退行性疾病的发病率正在上升，而且无法预防或治愈。如果它们具有共同的致病机制，那么针对这些机制的治疗方法可能对多种疾病都有益处。tau 蛋白与多种神经退行性疾病的发病机制有关，包括阿尔茨海默病（AD）和帕金森病（PD）。tau 蛋白减少可预防多种 AD 小鼠模型中的认知缺陷、行为异常和其他病理变化。在这里，我们研究了 tau 蛋白减少是否也能预防两种 PD 小鼠模型的运动缺陷和病理改变，这两种模型是通过单侧纹状体注射 6-羟多巴胺（6-OHDA）或转导介导的人野生型α-突触核蛋白神经元表达产生的。在各种运动测试中，我们在 Tau(+/+)、Tau(+/-)和 Tau(-/-)背景下对这两种模型进行了评估。tau 蛋白减少并不能预防 6-OHDA 引起的运动缺陷，而且还略微加重了其中一种缺陷。tau 蛋白减少也不能预防 6-OHDA 诱导的纹状体多巴胺能末梢丧失。同样，tau 蛋白减少也不能预防α-突触核蛋白转基因小鼠的运动缺陷。我们的结果表明，tau 在 AD 和 PD 的发病机制中具有不同的作用，tau 蛋白减少可能对后者没有益处。
