Apolipoprotein E: structure determines function-from atherosclerosis to Alzheimer's disease to AIDS
Mahley RW, Weisgraber KH, Huang Y.
J Lipid Res. 2008 Dec 22.
ABSTRACTApolipoprotein (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. 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.Biohappiness
Eugenics before Galton
The literature of eugenics
Germline genetic engineering
Preimplantation genetic diagnosis
A life without pain? Hedonists take note'
Francis Galton and contemporary eugenics
Gene therapy and performance enhancement
Cathepsin D, HLA-DRB1 and APO and intelligence
and further reading
The Good Drug Guide
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
MDMA: Utopian Pharmacology
Critique of Huxley's Brave New World