Apolipoprotein E: from lipid transport to neurobiology.
Apolipoprotein E: from lipid transport to neurobiology.
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DOI：
10.1016/j.plipres.2010.09.001
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发表时间：
2011-01
影响因子：
13.6
通讯作者：
Ryan, Robert O.
中科院分区：
文献类型：
--
作者：
Hauser, Paul S.;Narayanaswami, Vasanthy;Ryan, Robert O.
载脂蛋白E作为一种脂质转运蛋白有着悠久的历史。胆固醇稳态和脂蛋白从循环中清除之间的整体关联与apoE作为低密度脂蛋白受体家族的细胞表面受体的配体的功能密切相关。apoE的受体结合特性受到亚型特异性氨基酸差异以及蛋白质脂化状态的强烈影响。随着对apoE作为循环血浆脂蛋白的结构组分的理解的发展，神经生物学的令人兴奋的发展重新引起了人们对apoE的兴趣。apoE4亚型与发病年龄和阿尔茨海默病风险增加之间的强而持久的相关性使apoE成为神经生物学的前沿。使用为研究apoE脂蛋白代谢而产生的遗传工具，转基因“敲入”和基因破坏小鼠现在是研究其在各种神经退行性疾病中的作用的优选模型。apoE和同种型特异性差异的关键结构知识正在推动旨在阐明单个氨基酸变化如何表现出如此深刻的重大病理后果的研究活动。本文综述了载脂蛋白E通过透镜的结构为基础的知识，导致假说，试图解释apoE的功能和异构体的具体影响有关的疾病机制。
Apolipoprotein (apo) E has a storied history as a lipid transport protein. The integral association between cholesterol homeostasis and lipoprotein clearance from circulation are intimately related to apoE's function as a ligand for cell surface receptors of the low density lipoprotein receptor family. The receptor binding properties of apoE are strongly influenced by isoform specific amino acid differences as well as the lipidation state of the protein. As understanding of apoE as a structural component of circulating plasma lipoproteins has evolved, exciting developments in neurobiology have revitalized interest in apoE. The strong and enduring correlation between the apoE4 isoform and age of onset and increased risk of Alzheimer's disease has catapulted apoE to the forefront of neurobiology. Using genetic tools generated for study of apoE lipoprotein metabolism, transgenic “knock-in” and gene-disrupted mice are now favored models for study of its role in a variety of neurodegenerative diseases. Key structural knowledge of apoE and isoform specific differences is driving research activity designed to elucidate how a single amino acid change can manifest such profoundly significant pathological consequences. This review describes apoE through a lens of structure-based knowledge that leads to hypotheses that attempt to explain the functions of apoE and isoform specific effects relating to disease mechanism.
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