Full-length apolipoprotein E protects against the neurotoxicity of an apoE-related peptide.
Apolipoprotein E was found to protect against the neurotoxic effects of a dimeric peptide derived from the receptor-binding region of this protein (residues 141-149). Both apoE3 and apoE4 conferred protection but the major N-terminal fragment of each isoform did not. Nor was significant protection provided by bovine serum albumin or apoA-I. Full-length apoE3 and apoE4 also inhibited the uptake of a fluorescent-labeled derivative of the peptide, suggesting that the mechanism of inhibition might involve competition for cell surface receptors/proteoglycans that mediate endocytosis and/or signaling pathways. These results might bear on the question of the role of apoE in neuronal degeneration, such as occurs in Alzheimer's disease where apoE4 confers a significantly greater risk of pathology.
Crutcher
K A
KA
Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA. crutchka@me.com
Lilley
H N
HN
Anthony
S R
SR
Zhou
W
W
Narayanaswami
V
V
D000818:Animals; D053318:Apolipoprotein E3 / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D005453:Fluorescence; D006493:Heparin / Q000378:metabolism; D008857:Microscopy, Interference; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D020033:Protein Isoforms; D006493:Heparin