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首页> 外文期刊>Glia >Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury
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Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury

机译：颅脑外伤后活化星形胶质细胞和小胶质细胞中γ-分泌酶成分早老素-1和尼卡斯特林的表达增加

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摘要

gamma-Secretase is an aspartyl protease composed of four proteins: presenilin (PS), nicastrin (Net), APH1, and PEN2. These proteins assemble into a membrane complex that cleaves a variety of substrates within the transmembrane domain. The gamma-secretase cleavage products play an important role in various biological processes such as embryonic development and Alzheimer's disease (AD). The major role of gamma-secretase in brain pathology has been linked to AD and to the production of the amyloid P-peptide. However, little is known about the possible role of gamma-secretase following acute brain insult. Here we examined by immunostaining the expression patterns of two gamma-secretase components, PSI and Net, in three paradigms of brain insult in mice: closed head injury, intracerebroventricular injection of LPS, and brain stabbing. Our results show that in naive and sham-injured brains expression of PS1 and Net is restricted mainly to neurons. However, following insult, the expression of both proteins is also observed in nonneuronal cells, consisting of activated astrocytes and microglia. Furthermore, the proteins are coexpressed within the same astrocytes and microglia, implying that these cells exhibit an enhanced gamma-secretase activity following brain damage. In view of the important role played by astrocytes and microglia in brain disorders, our findings suggest that gamma-secretase may participate in brain damage and repair processes by regulating astrocyte and microglia activation and/or function. (C) 2008 Wiley-Liss, Inc.
机译：γ-分泌酶是一种天冬氨酰蛋白酶，由四种蛋白质组成：早老素（PS），尼卡斯汀（Net），APH1和PEN2。这些蛋白质组装成膜复合物，该复合物在跨膜结构域内切割多种底物。 γ-分泌酶裂解产物在诸如胚胎发育和阿尔茨海默氏病（AD）的各种生物过程中起重要作用。 γ-分泌酶在脑病理学中的主要作用与AD和淀粉样蛋白P肽的产生有关。但是，人们对急性脑损伤后γ-分泌酶的可能作用了解甚少。在这里，我们通过免疫染色在小鼠脑部损伤的三种范例中对两种γ-分泌酶成分PSI和Net的表达模式进行了检查：闭合性颅脑损伤，脑室内注射LPS和刺伤大脑。我们的结果表明，在幼稚和假手术的大脑中，PS1和Net的表达主要限于神经元。然而，在侮辱之后，在由活化星形胶质细胞和小胶质细胞组成的非神经元细胞中也观察到了两种蛋白的表达。此外，这些蛋白质在相同的星形胶质细胞和小胶质细胞内共表达，这意味着这些细胞在脑损伤后表现出增强的γ-分泌酶活性。考虑到星形胶质细胞和小胶质细胞在脑部疾病中的重要作用，我们的发现表明，γ-分泌酶可能通过调节星形胶质细胞和小胶质细胞的激活和/或功能参与脑损伤和修复过程。 （C）2008 Wiley-Liss，Inc.

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