Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy.

Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy.
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DOI:
10.1038/nrn2620
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发表时间:
2009-05
影响因子:
34.7
通讯作者:
Bu, Guojun
Bu, Guojun
中科院分区:
医学1区
文献类型:
--
作者:
Bu, Guojun

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绝大多数阿尔茨海默病(AD)病例是迟发性的,其发展可能受到遗传和环境风险因素的影响。晚发性AD的一个强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,并通过apoE受体直接调节脑脂质代谢和突触功能,参与AD的发病过程。关于apoE对AD病理生理学的贡献的新知识为AD治疗提供了新的机会。
The vast majority of Alzheimer’s disease (AD) cases are late-onset and their development is likely influenced by both genetic and environmental risk factors. A strong genetic risk factor for late-onset AD is the presence of the ε4 allele of the apolipoprotein E (APOE) gene, which encodes a protein with crucial roles in cholesterol metabolism. Mounting evidence demonstrates that apoE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-β peptide and by directly regulating brain lipid metabolism and synaptic functions through apoE receptors. Emerging knowledge on the contribution of apoE to the pathophysiology of AD presents new opportunities for AD therapy.
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