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Activation of LXR by T0901317 Causes an Increases in DBP and CYP46 Expression and a Decrease in Aβ Level in Mouse Brains
Author: YangYuan
Tutor: JiangLingLing
School: Hebei Medical University
Course: Biochemistry and Molecular Biology
Keywords: Hepatic solitary Nuclear receptor D- bifunctional protein Cholesterol - 24S - hydroxylase Cholesterol beta - starch -like protein TO901317
CLC: R749.16
Type: Master's thesis
Year: 2005
Downloads: 71
Quote: 0
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Abstract
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Purpose : the deposition of beta - amyloid protein (beta-amyloid peptide, Aβ) is a key factor for the development of Alzheimer's disease ( Alzheimer 's disease , AD ) . Studies have shown that Aβ generation and precipitation of cholesterol metabolism are closely related . Inhibit cholesterol synthesis, and can significantly reduce the generation of Aβ and the incidence of AD ; hypercholesterolemia can increase brain Aβ immunoreactivity . Therefore, in recent years , the relationship of brain cholesterol metabolism disorder and Aβ generation became a research focus. Nuclear receptor LXR (liver X-activated receptor) in the brain tissue , is a key regulator of sites that control brain cholesterol flux . TO901317 is a chemical synthetic LXR ligands . The study found that the binding of the ligand and LXR activation of the ATP cassette transporter (ATP-binding cassette transporter, ABC) ABCA1, ABCG1 cholesterol metabolism downstream genes, to maintain the balance of the brain cholesterol library . APP23 transgenic mice overall experiments and C57BL / 6 mouse neurons in cell culture experiments have shown : with TO901317 , 22R - hydroxy cholesterol activate LXR , ABCA1 expression increased Aβ levels drop . But the overall level of normal mice to be LXR agonist , brain Aβ how changes have not been reported . The brain cholesterol through the blood-brain barrier into the blood, converted into bile acids to the liver is an important way to maintain the balance of brain cholesterol . The study showed that the majority of brain cholesterol by cholesterol - 24S - hydroxylase (cholesterol-24S-hydroxylase, CYP46) neurons within its conversion to the 24S - hydroxy- cholesterol through the blood-brain barrier . Activate LXR promotes cholesterol from the cells
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CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Cerebral organic mental disorder > Elderly as early as possible the old disorder
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