Full-length apolipoprotein E protects against the neurotoxicity of an apoE-related peptide

• Published in: Brain research Vol. 1306; pp. 106 - 115
• Main Authors: Crutcher, K.A, Lilley, H.N, Anthony, S.R, Zhou, W, Narayanaswami, V
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.01.2010; Elsevier
• Subjects: Adult and adolescent clinical studies; Alzheimer's disease; Animals; Apolipoprotein E3 - metabolism; Apolipoprotein E4 - metabolism; Apolipoproteins E - metabolism; Biological and medical sciences; Blotting, Western; Cell Death - physiology; Cell Survival - physiology; Cells, Cultured; Chick Embryo; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fluorescence; Heparin - metabolism; LRP; Medical sciences; Microscopy, Interference; Neurology; Neurons - physiology; Neuroprotection; Neurotoxicity; Organic mental disorders. Neuropsychology; Peptide Fragments - metabolism; Protein Isoforms - metabolism; Proteolysis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Neuroprotection; Neurotoxicity; LRP; Proteolysis; Alzheimer's disease; Nervous system diseases; Alzheimer disease; Cerebral disorder; Vertebrata; Apolipoprotein E; Length; Animal; Central nervous system disease; Degenerative disease; Chicken; Aves
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.10.021

Abstract 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.