Role of LXR and ABCA1 in the Pathogenesis of Alzheimers Disease -Implications for a New Therapeutic Approach

Radosveta      Koldamova; Iliya      Lefterov

doi:10.2174/156720507780362227

Abstract

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 β-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.

Keywords: Alzheimer's disease, Liver X Receptors, LXR ligands, ABCA1, APP transgenic mice, β-amyloid, Apo E, cholesterol