Cholesterol metabolism in Huntington disease

被引：120

作者：

Karasinska, Joanna M. ^{[1
]}

Hayden, Michael R. ^{[1
]}

机构：

[1] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada

来源：

NATURE REVIEWS NEUROLOGY | 2011年 / 7卷 / 10期

基金：

加拿大健康研究院;

关键词：

RECEPTOR-MEDIATED EXCITOTOXICITY; GLYCOGEN-SYNTHASE KINASE-3-BETA; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; LIVER-X-RECEPTORS; ALZHEIMERS-DISEASE; MOUSE MODEL; LIPID RAFTS; MUTANT HUNTINGTIN; APOLIPOPROTEIN-E;

D O I：

10.1038/nrneurol.2011.132

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

引用

页码：561 / 572

页数：12

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