文摘
Alzheimer鈥檚 disease (AD) is associated with impaired A尾 degradation in the brain. Enhancing the process of A尾 clearance is an attractive potential AD therapy. Treatment with LXR agonists may reduce A尾 levels in vivo. However, the clinical potential of many LXR agonists is limited because of their nonselective actions on LXR伪/尾, which lead to undesired hepatic lipogenesis via LXR伪-dependent pathways. In this study, ABCA1 up-regulators were identified from a series of flavonoids and were found to preferentially activate LXR尾 and up-regulate expression of ABCA1 and apoE in different cell lines. Further investigations confirmed that these compounds facilitate intracellular A尾 clearance in A尾-loaded BV2 cells. Administration of compound 19 reduced total brain A尾 and plaque burden in APP/PS1 double transgenic mice, associated with elevated ABCA1 and apoE expression. Compared with the nonselective LXR agonists, the active compounds reported here induced less accumulation of undesired lipids and triglycerides in HepG2 cells.