载脂蛋白E及其受体与阿尔茨海默病：途径、发病机制及治疗
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy.
作者信息
Bu Guojun
机构信息
Hope Center for Neurological Disorders, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
出版信息
Nat Rev Neurosci. 2009 May;10(5):333-44. doi: 10.1038/nrn2620. Epub 2009 Apr 2.
Abstract
The vast majority of Alzheimer's disease (AD) cases are late-onset and their development is probably influenced by both genetic and environmental risk factors. A strong genetic risk factor for late-onset AD is the presence of the epsilon4 allele of the apolipoprotein E (APOE) gene, which encodes a protein with crucial roles in cholesterol metabolism. There is mounting evidence that APOE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-beta peptide and by directly regulating brain lipid metabolism and synaptic functions through APOE receptors. Emerging knowledge of the contribution of APOE to the pathophysiology of AD presents new opportunities for AD therapy.
摘要
绝大多数阿尔茨海默病（AD）病例为晚发型，其发病可能受遗传和环境风险因素的双重影响。晚发型AD的一个强大遗传风险因素是载脂蛋白E（APOE）基因的ε4等位基因的存在，该基因编码一种在胆固醇代谢中起关键作用的蛋白质。越来越多的证据表明，APOE4通过调节淀粉样β肽的代谢和聚集，以及通过APOE受体直接调节脑脂质代谢和突触功能，从而促进AD的发病机制。APOE对AD病理生理学贡献的新认识为AD治疗带来了新机遇。
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Arch Gen Psychiatry. 2009 Jan;66(1):81-7. doi: 10.1001/archgenpsychiatry.2008.516.
2
Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease.脂蛋白受体与胆固醇在淀粉样前体蛋白转运及蛋白水解加工中的作用，对阿尔茨海默病的影响
Semin Cell Dev Biol. 2009 Apr;20(2):191-200. doi: 10.1016/j.semcdb.2008.10.005. Epub 2008 Oct 17.
3
Gamma-secretase limits the inflammatory response through the processing of LRP1.γ-分泌酶通过对低密度脂蛋白受体相关蛋白1（LRP1）的加工处理来限制炎症反应。
Sci Signal. 2008 Nov 25;1(47):ra15. doi: 10.1126/scisignal.1164263.
4
apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain.载脂蛋白E异构体特异性破坏小鼠脑内β淀粉样肽的清除。
J Clin Invest. 2008 Dec;118(12):4002-13. doi: 10.1172/JCI36663. Epub 2008 Nov 13.
5
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J Neurosci. 2008 Nov 5;28(45):11445-53. doi: 10.1523/JNEUROSCI.1972-08.2008.
6
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7
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8
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J Neurosci. 2008 Oct 8;28(41):10339-48. doi: 10.1523/JNEUROSCI.1917-08.2008.
9
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