Linked Life Data

17573819

Source:http://linkedlifedata.com/resource/pubmed/id/17573819

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-9-4
pubmed:abstractText
Aberrant cholesterol metabolism has been implicated in Alzheimer disease (AD) and other neurological disorders. Oxysterols and other cholesterol oxidation products are effective ligands of liver X activated receptor (LXR) nuclear receptors, major regulators of genes subserving cholesterol homeostasis. LXR receptors act as molecular sensors of cellular cholesterol concentrations and effectors of tissue cholesterol reduction. Following their interaction with oxysterols, activation of LXRs induces the expression of ATP-binding cassette, sub-family A member 1, a pivotal modulator of cholesterol efflux. The relative solubility of oxysterols facilitates lipid flux among brain compartments and egress across the blood-brain barrier. Oxysterol-mediated LXR activation induces local apoE biosynthesis (predominantly in astrocytes) further enhancing cholesterol re-distribution and removal. Activated LXRs invoke additional neuroprotective mechanisms, including induction of genes governing bile acid synthesis (sterol elimination pathway), apolipoprotein elaboration, and amyloid precursor protein processing. The latter translates into attenuated beta-amyloid production that may ameliorate amyloidogenic neurotoxicity in AD brain. Stress-induced up-regulation of the heme-degrading enzyme, heme oxygenase-1 in AD-affected astroglia may impact central lipid homeostasis by promoting the oxidation of cholesterol to a host of oxysterol intermediates. Synthetic oxysterol-mimetic drugs that activate LXR receptors within the CNS may provide novel therapeutics for management of AD and other neurological afflictions characterized by deranged tissue cholesterol homeostasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1727-37
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Oxysterols, cholesterol homeostasis, and Alzheimer disease.
pubmed:affiliation
Laboratory of Natural Medicinal Compounds, Migal-Galilee Technology Center, Kiryat-Shmona, Israel.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't