Study for the mechanism linking intracellular amyloid precursor protein transport and cholesterol metabolism

阿尔茨海默病的一个主要病理标志是淀粉样蛋白的积累？（A？）在老年斑中。A？由淀粉样前体蛋白（APP）产生。在这项研究中，我发现用24 S-羟基胆固醇（脑特异性氧化固醇）处理，通过未折叠蛋白反应途径诱导ER伴侣GRP 78的表达，并增强APP/GRP 78复合物的形成。因此，24 S-羟基胆固醇下调细胞内APP的运输，导致A？生产

A major pathological hallmark of Alzheimer’s disease is the accumulation of Amyloid ? (A?) in senile plaques. A? is generated from Amyloid precursor protein (APP). In this study, I found that the treatment with 24S-hydroxycholesterol, which is the brain-specific oxysterol, induced the expression of GRP78, an ER chaperone, through unfolded protein response pathways, and enhanced the formation of the APP/GRP78 complex. Thereby, 24S-hydroxycholesterol downregulates intracellular APP trafficking, resulting in the reduction of A? production.