Expression of the low-affinity nerve growth factor receptor enhances beta-amyloid peptide toxicity.
The low-affinity nerve growth factor receptor (NGFR) p75NGFR induces apoptosis in the absence of nerve growth factor (NGF) binding but enhances neural survival when bound by NGF. Basal forebrain cholinergic neurons express the highest levels of p75NGFR in the adult human brain and are preferentially involved in Alzheimer disease, raising the question of whether there may be a functional relationship between the expression of p75NGFR and basal forebrain cholinergic neuronal degeneration in Alzheimer disease. The expression of p75NGFR by wild-type and mutant PC12 cells potentiated cell death induced by beta-amyloid peptide. NGF binding to p75NGFR inhibited the toxicity of beta-amyloid peptide, whereas NGF binding to TrkA, the high-affinity NGFR, enhanced it. These results suggest a possible link between beta-amyloid peptide toxicity and preferential degeneration of cells expressing p75NGFR.
Rabizadeh
S
S
Department of Neurology, University of California, Los Angeles 90024.
Bitler
C M
CM
Butcher
L L
LL
Bredesen
D E
DE
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D016548:Prosencephalon / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D014162:Transfection
D016229:Amyloid beta-Peptides; D009414:Nerve Growth Factors; D009498:Neurotoxins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA