Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS

被引：420
作者：
Mahley, Robert W. [1 ,2 ,3 ,4 ,5 ]
Weisgraber, Karl H. [1 ,2 ,4 ,5 ]
Huang, Yadong [1 ,2 ,4 ]
机构：
[1] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA
[2] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
来源：
JOURNAL OF LIPID RESEARCH | 2009年 / 50卷
基金：
美国国家卫生研究院;
关键词：
cholesterol; neurodegeneration; HIV; coronary heart disease; LDL receptor; dysbetalipoproteinemia; heparan sulfate proteoglycans; infectious diseases; evolution; LOW-DENSITY LIPOPROTEINS; AMYLOID-BETA PEPTIDE; CELL-SURFACE RECEPTORS; AMINO-ACID-SEQUENCE; DOMAIN INTERACTION; TRANSGENIC MICE; III HYPERLIPOPROTEINEMIA; HUMAN FIBROBLASTS; NEURONAL CELLS; REMNANT LIPOPROTEINS;
D O I：
10.1194/jlr.R800069-JLR200
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Apolipoprotein (apo) E has roles beyond lipoprotein metabolism. The detrimental effects of apoE4 in cardiovascular, neurological, and infectious diseases correlate with its structural features (e.g., domain interaction) that distinguish it from apoE3 and apoE2. Structure/function studies revealed that apoE2 is severely defective in LDL receptor binding because of a structural difference that alters the receptor binding region and helped unravel the mechanism of type III hyperlipoproteinemia. ApoE4 is the major genetic risk factor for Alzheimer's disease and sets the stage for neuropathological disorders precipitated by genetic, metabolic, and environmental stressors. ApoE also influences susceptibility to parasitic, bacterial, and viral infections. In HIV-positive patients, apoE4 homozygosity hastens progression to AIDS and death and increases susceptibility to opportunistic infections. jlr The next phase in our understanding of apoE will be characterized by clinical intervention to prevent or reverse the detrimental effects of apoE4 by modulating its structure or blocking the pathological processes it mediates.-Mahley, R. W., K. H. Weisgraber, and Y. Huang. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS. J. Lipid Res. 2009. S183-S188.
引用
收藏
页码：S183 / S188
页数：6
相关论文
共 57 条
[1]   Two hepatic enhancers, HCR.1 and HCR.2, coordinate the liver expression of the entire human apolipoprotein E/C-I/C-IV/C-II gene cluster [J].
Allan, CM ;
Taylor, S ;
Taylor, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (46) :29113-29119
[2]   Neuron-specific apolipoprotein E4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice [J].
Brecht, WJ ;
Harris, FM ;
Chang, SJ ;
Tesseur, I ;
Yu, GQ ;
Xu, Q ;
Fish, JD ;
Wyss-Coray, T ;
Buttini, M ;
Mucke, L ;
Mahley, RW ;
Huang, YD .
JOURNAL OF NEUROSCIENCE, 2004, 24 (10) :2527-2534
[3]   Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons [J].
Brodbeck, Jens ;
Balestra, Maureen E. ;
Saunders, Ann M. ;
Roses, Allen D. ;
Mahley, Robert W. ;
Huang, Yadong .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (04) :1343-1346
[4]   Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE ε4/ε4 genotype accelerates HIV disease progression [J].
Burt, Trevor D. ;
Agan, Brian K. ;
Marconi, Vincent C. ;
He, Weijing ;
Kulkarni, Hemant ;
Mold, Jeffrey E. ;
Cavrois, Marielle ;
Huang, Yadong ;
Mahley, Robert W. ;
Dolan, Matthew J. ;
McCune, Joseph M. ;
Ahuja, Sunil K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (25) :8718-8723
[5]   Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity [J].
Chang, SJ ;
Ma, TR ;
Miranda, RD ;
Balestra, ME ;
Mahley, RW ;
Huang, YD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (51) :18694-18699
[6]   GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].
CORDER, EH ;
SAUNDERS, AM ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
SCIENCE, 1993, 261 (5123) :921-923
[7]  
de Bont N, 1999, J LIPID RES, V40, P680
[8]   Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia [J].
Dong, LM ;
Parkin, S ;
Trakhanov, SD ;
Rupp, B ;
Simmons, T ;
Arnold, KS ;
Newhouse, YM ;
Innerarity, TL ;
Weisgraber, KH .
NATURE STRUCTURAL BIOLOGY, 1996, 3 (08) :718-722
[9]  
DONG LM, 1994, J BIOL CHEM, V269, P22358
[10]   Human apolipoprotein E4 domain interaction - Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins [J].
Dong, LM ;
Weisgraber, KH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (32) :19053-19057
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