Tu Jian, Chen Baian, Yang Lifeng, Qi Kezong, Lu Jing, Zhao Deming
State Key Laboratories for Agrobiotechnology, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, 100193, Beijing, China,
J Mol Neurosci. 2015 Jun;56(2):509-18. doi: 10.1007/s12031-015-0553-2. Epub 2015 Apr 14.
Prions are the only convincingly demonstrated proteinaceous infectious particle, yet recent studies find that amyloid-β peptide (Aβ) aggregates are capable of self-propagation, which induces amyloidosis pathology in Alzheimer's disease (AD) model mice that is similar to the self-propagation phenomenon of prions in neurons. Gliosis is a common hallmark of AD and prion diseases, in which activated microglia accumulate around abnormal protein deposits. Analyses of the characteristics of activated microglia induced by Aβ in comparison with those induced by prions will provide new insight into the pathogenesis of AD. Therefore, we compared the characteristics of BV-2 cells (model microglia) activated by Aβ fibrillar peptides (Aβ1-42) and prions (PrP106-126). Aβ1-42 and PrP106-126, as well as the supernatants of the media collected from BV-2 cells cocultured with Aβ1-42 and PrP106-126, were potent activators of BV-2 microglial activity, but the chemotaxis index (CI) induced by Aβ1-42 was significantly higher than that induced by PrP106-126 at each concentration. Aβ1-42 and PrP106-126 increased the proliferation index (PI) and upregulated monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (TGF-β1) expression after 12 h of exposure. Our results show that Aβ activates microglia and regulates microglial protein expression in a manner similar to prions and, thus, provide new insight into the pathogenesis of AD.
朊病毒是唯一经确凿证实的蛋白质传染性颗粒，但最近的研究发现，淀粉样β肽（Aβ）聚集体能够自我增殖，这在阿尔茨海默病（AD）模型小鼠中诱发了淀粉样变性病理，类似于朊病毒在神经元中的自我增殖现象。胶质细胞增生是AD和朊病毒疾病的共同特征，其中活化的小胶质细胞在异常蛋白质沉积物周围积聚。将Aβ诱导的活化小胶质细胞的特征与朊病毒诱导的特征进行分析，将为AD的发病机制提供新的见解。因此，我们比较了由Aβ纤维状肽（Aβ1-42）和朊病毒（PrP106-126）激活的BV-2细胞（小胶质细胞模型）的特征。Aβ1-42和PrP106-126，以及与Aβ1-42和PrP106-126共培养的BV-2细胞收集的培养基上清液，都是BV-2小胶质细胞活性的有效激活剂，但在每个浓度下，Aβ1-42诱导的趋化指数（CI）显著高于PrP106-126诱导的趋化指数。暴露12小时后，Aβ1-42和PrP106-126增加了增殖指数（PI），并上调了单核细胞趋化蛋白-1（MCP-1）和转化生长因子β1（TGF-β1）的表达。我们的结果表明，Aβ以类似于朊病毒的方式激活小胶质细胞并调节小胶质细胞蛋白表达，从而为AD的发病机制提供了新的见解。
