Induction of the Cholesterol Transporter ABCA1 in Central Nervous System Cells by Liver X Receptor Agonists Increases Secreted Aβ Levels

摘要: The expression, function, and regulation of the cholesterol efflux molecule, ABCA1, has been extensively examined in peripheral tissues but only poorly studied brain. Brain metabolism is interest because several lines evidence suggest that elevated increases risk Alzheimer's disease. We found a largely neuronal expression ABCA1 normal rat brain by situ hybridization. message was dramatically up-regulated neurons glia areas damage hippocampal AMPA lesion after 3–7 days. Immunoblot analysis demonstrated protein cultured glial cells, induced ligands nuclear hormone receptors retinoid X receptor liver family. treatment with retinoic acid oxysterols, including 22(R)-hydroxycholesterol 24-hydroxycholesterol. Expression an ABCA1-green fluorescent construct neuroblastoma cells fluorescence perinuclear compartments on plasma membrane. Because Aβ peptide important disease pathogenesis, we whether induction altered levels. Treatment caused significant secreted Aβ40 (29%) Aβ42 (65%). nonsteroidal ligand, TO-901317, similarly increased levels (25%) (126%). increase reduced RNAi blocking expression. These data molecule may also be involved secretion membrane-associated Aβ.