Ahn Sung-Min, Byun Kyunghee, Cho Kun, Kim Jin Young, Yoo Jong Shin, Kim Deokhoon, Paek Sun Ha, Kim Seung U, Simpson Richard J, Lee Bonghee
Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea.
PLoS One. 2008 Jul 30;3(7):e2829. doi: 10.1371/journal.pone.0002829.
Albumin, an abundant plasma protein with multifunctional properties, is mainly synthesized in the liver. Albumin has been implicated in Alzheimer's disease (AD) since it can bind to and transport amyloid beta (Abeta), the causative agent of AD; albumin is also a potent inhibitor of Abeta polymerization. Despite evidence of non-hepatic transcription of albumin in many tissues including kidney and pancreas, non-hepatic synthesis of albumin at the protein level has been rarely confirmed. In a pilot phase study of Human Brain Proteome Project, we found evidence that microglial cells in brain may synthesize albumin. Here we report, for the first time, the de novo synthesis of albumin in human microglial cells in brain. Furthermore, we demonstrate that the synthesis and secretion of albumin from microglial cells is enhanced upon microglial activation by Abeta(1-42)- or lipopolysaccharide (LPS)-treatment. These data indicate that microglial cells may play a beneficial role in AD by secreting albumin that not only inhibits Abeta polymerization but also increases its clearance.
白蛋白是一种具有多种功能特性的丰富血浆蛋白，主要在肝脏中合成。白蛋白与阿尔茨海默病（AD）有关，因为它可以结合并转运AD的致病因子淀粉样β蛋白（Aβ）；白蛋白也是Aβ聚合的有效抑制剂。尽管在包括肾脏和胰腺在内的许多组织中都有白蛋白非肝脏转录的证据，但在蛋白质水平上白蛋白的非肝脏合成很少得到证实。在人类脑蛋白质组计划的一项试点阶段研究中，我们发现了大脑中的小胶质细胞可能合成白蛋白的证据。在此，我们首次报告了人类大脑小胶质细胞中白蛋白的从头合成。此外，我们证明，用Aβ（1-42）或脂多糖（LPS）处理激活小胶质细胞后，小胶质细胞中白蛋白的合成和分泌会增强。这些数据表明，小胶质细胞可能通过分泌白蛋白在AD中发挥有益作用，白蛋白不仅能抑制Aβ聚合，还能增加其清除率。
