期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1801, 期 8, 页码 824-830出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2010.02.010
关键词
Alzheimer's disease; ABCA1; Liver X Receptor; Cell cholesterol transport; APOE; Animal model; Amyloid deposition; Cognitive impairment
资金
- NIA [AG031956, AG027973]
- Alzheimer's Drug Discovery Foundation
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 A beta 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 A beta aggregation and amyloid clearance. This review will summarize the results of research on ABCA1, particularly related to AD and neurodegeneration. (C) 2010 Published by Elsevier B.V.
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