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Biochim Biophys Acta. 2010 Aug;1801(8):824-30. doi: 10.1016/j.bbalip.2010.02.010. Epub 2010 Feb 24.

The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration.

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1
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. radak@pitt.edu

Abstract

ATP-binding cassette transporter A1 - ABCA1, is the most extensively studied transporter in human pathology. ABCA1 became a primary subject of research in many academic and pharmaceutical laboratories immediately after the discovery that mutations at the gene locus cause severe familial High Density Lipoprotein (HDL) deficiency and, in the homozygous form - Tangier disease. The protein is the major regulator of intracellular cholesterol efflux which is the initial and essential step in the biogenesis and formation of nascent HDL particles. The transcriptional regulation of ABCA1 by nuclear Liver X Receptors (LXR) provided a starting point for drug discovery and development of synthetic LXR ligands/ABCA1 activators for treatment of arteriosclerosis. A series of reports that revealed the role of ABCA1 in Abeta deposition and clearance, as well as the possibility for association of some ABCA1 genetic variants with risk for Alzheimer's disease (AD) brought a new dimension to ABCA1 research. The LXR-ABCA1-APOE regulatory axis is now considered a promising therapeutic target in AD, which includes the only proven risk factor for AD - APOE, at two distinct levels - transcriptional regulation by LXR, and ABCA1 controlled lipidation which can influence Abeta aggregation and amyloid clearance. This review will summarize the results of research on ABCA1, particularly related to AD and neurodegeneration.

PMID:
20188211
PMCID:
PMC3712769
DOI:
10.1016/j.bbalip.2010.02.010
[Indexed for MEDLINE]
Free PMC Article
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