Role of LXR and ABCA1 in the pathogenesis of Alzheimer's disease implications for a new therapeutic approach
Role of LXR and ABCA1 in the pathogenesis of Alzheimer's disease implications for a new therapeutic approach
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DOI：
10.2174/156720507780362227
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发表时间：
2007-04-01
影响因子：
2.1
通讯作者：
Lefterov, Iliya
中科院分区：
文献类型：
--
作者：
Koldamova, Radosveta;Lefterov, Iliya
从流行病学研究到体外和体内实验研究都提供了令人信服的证据，表明脑脂质代谢的不同方面可能通过影响β -淀粉样蛋白的沉积和清除来影响阿尔茨海默病的发病机制。已经证明，被称为核肝X受体（LXR）的转录因子及其应答基因提供了自然的调节机制，并通过其对细胞内胆固醇含量、胆固醇外流的调节作用以及可能通过抗炎机制影响阿尔茨海默病的发病机制。在此，我们简要总结了不同研究小组所采取的方法，这些方法形成了如今关于LXR和ABCA1在脑淀粉样蛋白生成和淀粉样蛋白清除中的调节作用的工作模型，并且我们强调了LXR激动剂的治疗潜力。
Studies, ranging from epidemiological to in vitro and in vivo experimental settings have provided convincing evidence that different aspects of brain lipid metabolism may influence Alzheimer disease pathogenesis through effects on P-amyloid deposition and clearance. It has been demonstrated that transcription factors called nuclear liver X receptors (LXR) and their responsive genes provide natural regulatory mechanisms and influence AD pathogenesis through their modulatory effects on intracellular cholesterol content, cholesterol efflux and possibly via anti-inflammatory mechanisms. Here, we provide a brief summary of the approaches undertaken by different groups that lead to the nowadays working model of LXR and ABCA1 regulatory role in brain amyloidogenesis and amyloid clearance and we highlight the therapeutic potential of LXR agonists.