Tau phosphorylation increases in symptomatic mice overexpressing A30P α-synuclein
Tau phosphorylation increases in symptomatic mice overexpressing A30P α-synuclein
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DOI：
10.1016/j.expneurol.2004.07.016
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发表时间：
2005-04-01
影响因子：
5.3
通讯作者：
Wolozin, B
中科院分区：
文献类型：
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作者：
Frasier, M;Walzer, M;Wolozin, B
过度表达突变的α-突触核蛋白的小鼠会出现进行性的运动功能丧失，这与脑干神经元中聚集的α-突触核蛋白的聚集有关。最近的报道表明，tau的病理可能也与帕金森病(PD)和α-突触核蛋白的聚集有关。我们现在报告，过度表达A30Pα-突触核蛋白的小鼠在聚集的α-突触核蛋白积累的同时，会出现异常的磷酸化tau。Tau的增强磷酸化只在有症状的小鼠身上发生，这些小鼠也含有丰富的聚集的α-突触核蛋白。免疫印迹和抗体PHF-1和AT8的免疫细胞化学研究表明，tau的磷酸化增加发生在S396/404和S202。聚集α-突触核蛋白的神经元出现在脑干背侧，与tau蛋白异常磷酸化的神经元没有强烈的共存，而tau蛋白异常磷酸化主要发生在脑干腹侧。α-突触核蛋白的聚集和tau的磷酸化与磷酸化c-jun激酶(JNK)水平的增加有关，JNK是一种已知的磷酸化tau蛋白的应激蛋白。这些结果表明，α-突触核蛋白病理可以刺激tau的早期病变。(C)2004 Elsevier Inc.保留所有权利。
Mice overexpressing mutant alpha-synuclein develop a progressive loss of motor function associated with the accumulation of aggregated alpha-synuclein in neurons of the brainstem. Recent reports suggest that tau pathology might also be associated with Parkinson disease (PD) and aggregation of alpha-synuclein. We now report that mice overexpressing A30P alpha-synuclein develop abnormally phosphorylated tau in parallel with the accumulation of aggregated alpha-synuclein. Enhanced phosphorylation of tau occurs only in symptomatic mice that also harbor abundant aggregated alpha-synuclein. The increased phosphorylation of tau occurs at S396/404 and S202 as shown by immunoblotting and immunocytochemical studies with the antibodies PHF-1 and AT8. Neurons that accumulated alpha-synuclein occurred in the dorsal brainstem and did not show strong colocalization with neurons that showed abnormal tau phosphorylation, which largely occurred in the ventral brainstem. Aggregation of a-synuclein and phosphorylation of tau are associated with increased levels of phosphorylated c-jun kinase (JNK), which is a stress kinase known to phosphorylate tau protein. These results suggest that alpha-synuclein pathology can stimulate early pathological changes in tau. (c) 2004 Elsevier Inc. All rights reserved.