Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease.
Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease.
复制标题
DOI：
10.1371/journal.pone.0029257
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mucke L
中科院分区：
文献类型：
--
作者：
Morris M;Koyama A;Masliah E;Mucke L
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，针对这些机制的治疗可能在多种情况下有益。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蛋白减少可防止多种AD小鼠模型的认知缺陷、行为异常和其他病理改变。本研究在单侧纹状体注射6-羟多巴胺（6-OHDA）或转基因介导的人类野生型α-突触核蛋白的神经元表达两种PD小鼠模型中，研究了tau蛋白减少是否也能预防运动缺陷和病理改变。在各种运动测试中对两种模型的Tau +/+， Tau +/ -和Tau - / -背景进行评估。Tau蛋白的减少并不能预防6-OHDA引起的运动缺陷，并使其中一项运动缺陷稍微恶化。Tau蛋白的减少也不能阻止6-羟多巴胺诱导的纹状体多巴胺末端的丧失。同样，tau蛋白的减少也不能防止α-突触核蛋白转基因小鼠的运动缺陷。我们的研究结果表明，tau蛋白在AD和PD的发病机制中具有不同的作用，而tau蛋白的减少可能对后者没有好处。
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.
登录
查看更多内容
依赖性β-淀粉样蛋白引发的tau依赖性微管拆卸。
DOI：
10.1083/jcb.200605187
发表时间：
2006-11-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
King ME;Kan HM;Baas PW;Erisir A;Glabe CG;Bloom GS
通讯作者：
Bloom GS
影响因子：
5.3
作者：
Frasier, M;Walzer, M;Wolozin, B
通讯作者：
Wolozin, B
影响因子：
9.9
作者：
DITTER, SM;MIRRA, SS
通讯作者：
MIRRA, SS
影响因子：
16.2
作者：
KONDO, J;HONDA, T;IHARA, Y
通讯作者：
IHARA, Y
影响因子：
168.9
作者：
Ferri, CP;Prince, M;Scazufca, M
通讯作者：
Scazufca, M