Department of Neurology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
Brain Res. 2011 Sep 2;1410:12-23. doi: 10.1016/j.brainres.2011.06.064. Epub 2011 Jul 7.
Hyperphosphorylated tau protein constitutes a significant portion of intracellular inclusions in some neurodegenerative diseases. In addition, mutations in tau protein cause familial forms of frontotemporal dementia (FTD), indicating that dysfunction of tau protein is responsible for neurodegeneration and dementia. P301S tau-transgenic (Tg) mouse expressing human mutant tau in neurons exhibits similar features of human tauopathies including neuronal degeneration and filament accumulation consisted of hyperphosphorylated tau protein. In the present study, we attempted to characterize protein expression profiles in P301S tau-Tg mouse by using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled by peptide mass fingerprinting (PMF). As a result, we identified four upregulated proteins; heat shock protein 27 (Hsp27), peroxiredoxin 6 (Prdx6), apolipoprotein E (ApoE), and latexin (LTXN), all of which may function as a neuroprotective mechanism against tau toxicity. In immunohistochemistry, these four proteins were increased invariably in astrocytes, and these astrocytes infiltrated the area in which there are numerous accumulations of hyperphosphorylated tau and neuronal loss. Therefore, these results may indicate that astrocytes provide a neuroprotective mechanism against tau toxicity.
过度磷酸化的 tau 蛋白构成了一些神经退行性疾病中细胞内包涵体的重要组成部分。此外，tau 蛋白的突变导致额颞叶痴呆（FTD）的家族形式，表明 tau 蛋白的功能障碍是神经退行性变和痴呆的原因。在神经元中表达人突变 tau 的 P301S tau 转基因（Tg）小鼠表现出类似于人类 tau 病的特征，包括神经元变性和由过度磷酸化的 tau 蛋白组成的纤维积累。在本研究中，我们试图通过二维差异凝胶电泳（2D-DIGE）结合肽质量指纹图谱（PMF）来描述 P301S tau-Tg 小鼠的蛋白质表达谱。结果，我们鉴定出了四个上调蛋白：热休克蛋白 27（Hsp27）、过氧化物还原酶 6（Prdx6）、载脂蛋白 E（ApoE）和 Latexin（LTXN），它们都可能作为一种针对 tau 毒性的神经保护机制。在免疫组织化学中，这四种蛋白质在星形胶质细胞中始终增加，这些星形胶质细胞浸润在大量过度磷酸化的 tau 和神经元丢失的区域。因此，这些结果可能表明星形胶质细胞提供了一种针对 tau 毒性的神经保护机制。
