Rowland Institute at Harvard University, Cambridge, MA, 02142, United States.
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, United States.
Sci Rep. 2017 Jul 18;7(1):5722. doi: 10.1038/s41598-017-05619-z.
Considerable evidence shows critical roles of intracellular pathogenic events of Alzheimer's disease (AD). In particular, intracellular amyloid-β accumulation and oligomerization are early AD pathologic processes, which may lead to changes in inflammatory molecules and other AD-related pathological components. Curcumin and its analogs have been identified as potential drug candidates for AD. However, the effects of curcumin on intracellular AD pathologic processes remain largely unknown. Here we utilized a recently developed nanoplasmonic fiber tip probe (nFTP) technology and investigated whether curcumin leads to intracellular AD pathologic changes. We showed that our nFTP technology could robustly detect intracellular AD-related protein changes caused by a well-known inflammation inducer and a familial AD mutation. Intriguingly, curcumin remarkably reduced the level of intracellular oligomers while modestly reduced the level of an inflammatory cytokine. Thus, our results provided evidence that curcumin's mechanism of action in attenuating AD pathology is through a major role of decreasing oligomerization.
大量证据表明阿尔茨海默病(AD)的细胞内致病事件起着重要作用。特别是,细胞内淀粉样β的积累和寡聚化是 AD 的早期病理过程,这可能导致炎症分子和其他与 AD 相关的病理成分发生变化。姜黄素及其类似物已被确定为 AD 的潜在药物候选物。然而,姜黄素对细胞内 AD 病理过程的影响在很大程度上仍不清楚。在这里,我们利用了一种新开发的纳米等离子体光纤尖端探针(nFTP)技术,研究了姜黄素是否会导致细胞内 AD 病理变化。我们表明,我们的 nFTP 技术可以稳健地检测由已知的炎症诱导剂和家族性 AD 突变引起的细胞内 AD 相关蛋白变化。有趣的是,姜黄素显著降低了细胞内寡聚物的水平,而对炎症细胞因子的水平仅有适度降低。因此,我们的结果提供了证据,表明姜黄素减轻 AD 病理的作用机制是通过减少寡聚化发挥主要作用。