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Induction of cholesterol efflux in the CNS

Author(s): G. William Rebeck

Journal: Neurobiology of Lipids
ISSN 1683-5506

Volume: 3;
Start page: 1;
Date: 2004;
Original page

Keywords: apolipoprotein | apoE | ABC-A1 | LXR | oxysterols | Alzheimer's disease | cholesterol homeostasis efflux | neurodegeneration | lipoprotein | apolipoprotein | LRP | Down' syndrome | ApoE4 | HMGCoA reductase | lipids | LDLr | LRP receptor | injury | Niemann Pick C (NPC)

Intricate cellular mechanisms exist for maintaining proper cholesterol levels. Several recent studies of removal of excess cholesterol in the CNS have focused on the ABC-A1 lipid transporter and its regulation via the LXR nuclear hormone receptor. Cellular cholesterol is hydroxylated to form oxysterols (24-hydroxycholesterol in the brain), which bind LXR and promote gene transcription. LXR activation increases levels of ABC-A1 and apoE, which together act to remove cholesterol and other lipids from cells. Recent studies including Liang et al. suggest manipulation of the LXR system alters brain cholesterol homeostasis and apoE levels, and thus could be beneficial in approaches to Alzheimer disease therapeutics.

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