Institute for Research in Biomedicine. Joint IRB-BSC Program in Computational Biology, Barcelona, Spain.
PLoS One. 2013;8(3):e58837. doi: 10.1371/journal.pone.0058837. Epub 2013 Mar 8.
A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the effect of lansoprazole, and other proton-pump inhibitors (PPIs), on Aβ production in AD cellular and animal models. We found that lansoprazole enhances Aβ37, Aβ40 and Aβ42 production and lowers Aβ38 levels on amyloid cell models. Interestingly, acute lansoprazole treatment in wild type and AD transgenic mice promoted higher Aβ40 levels in brain, indicating that lansoprazole may also exacerbate Aβ production in vivo. Overall, our data presents for the first time that PPIs can affect amyloid metabolism, both in vitro and in vivo.
阿尔茨海默病（AD）发病机制中的一个关键事件是淀粉样蛋白-β（Aβ）物质在大脑中的积累，这些物质来源于淀粉样前体蛋白（APP）被β-和γ-分泌酶的连续切割。基于一项用于 AD 药物再利用的系统生物学研究，我们探索了兰索拉唑和其他质子泵抑制剂（PPIs）对 AD 细胞和动物模型中 Aβ 产生的影响。我们发现兰索拉唑可增强淀粉样细胞模型中 Aβ37、Aβ40 和 Aβ42 的产生，并降低 Aβ38 的水平。有趣的是，在野生型和 AD 转基因小鼠中进行的兰索拉唑急性处理可促进大脑中 Aβ40 水平升高，表明兰索拉唑在体内也可能加剧 Aβ 的产生。总的来说，我们的数据首次表明，PPIs 可影响淀粉样代谢，无论是在体外还是体内。
