Role of LXR and ABCA1 in the pathogenesis of Alzheimer's disease - implications for a new therapeutic approach.
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 beta-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.
Koldamova
Radosveta
R
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. radak@pitt.edu
Lefterov
Iliya
I
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol