Role of LXR and ABCA1 in the Pathogenesis of Alzheimers Disease -Implications for a New Therapeutic Approach
Radosveta Koldamova and Iliya Lefterov
Affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Bridgeside Point, 100 Technology Dr., Pittsburgh, PA 15219,USA.
Keywords: Alzheimer's disease, Liver X Receptors, LXR ligands, ABCA1, APP transgenic mice, β-amyloid, Apo E, cholesterol
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.
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