Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.
Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.
复制标题
DOI：
10.3233/jad-2006-10101
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Laura Zhang;M. Fiala;J. Cashman;J. Sayre;Araceli Espinosa;Michelle Mahanian;Justin Zaghi;V. Badmaev;M. Graves;G. Bernard;M. Rosenthal
中科院分区：
文献类型：
--
作者：
Laura Zhang;M. Fiala;J. Cashman;J. Sayre;Araceli Espinosa;Michelle Mahanian;Justin Zaghi;V. Badmaev;M. Graves;G. Bernard;M. Rosenthal
阿尔茨海默病（AD）的治疗是困难的，由于其发病机制的无知。AD患者在先天免疫细胞、单核细胞/巨噬细胞体外吞噬淀粉样蛋白β（1-42）（Abeta）和清除Abeta斑块方面存在缺陷[5]。在动物模型中，天然产物姜黄素增强了Abeta的脑清除率。因此，我们在体外用类姜黄素处理6例AD患者和3例对照的巨噬细胞，并使用荧光和共聚焦显微镜测量Abeta摄取。在基线时，AD巨噬细胞摄取Abeta的强度显著低于对照巨噬细胞，并涉及表面结合，但无细胞内摄取。用姜黄素类物质处理巨噬细胞后，6名AD患者中的3名患者的巨噬细胞对Abeta的摄取显著增加（P<0.001至0.081）。AD巨噬细胞对类姜黄素反应的共聚焦显微镜显示在未处理的巨噬细胞中的表面结合，但在处理后与鬼笔环肽在细胞内室中共定位。姜黄素对先天免疫系统的免疫调节可能是一种安全的AD脑淀粉样变免疫清除方法。
Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42) (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain clearance of Abeta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using fluorescence and confocal microscopy. At baseline, the intensity of Abeta uptake by AD macrophages was significantly lower in comparison to control macrophages and involved surface binding but no intracellular uptake. After treatment of macrophages with curcuminoids, Abeta uptake by macrophages of three of the six AD patients was significantly (P<0.001 to 0.081) increased. Confocal microscopy of AD macrophages responsive to curcuminoids showed surface binding in untreated macrophages but co-localization with phalloidin in an intracellular compartment after treatment. Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in AD brain.