Expression of the low-affinity nerve growth factor receptor enhances beta-amyloid peptide toxicity.

Abstract

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 Alzhelmer 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 fi-amylold peptide. NGF binding to p75NGmr inhibited the toxicity of -amyloid peptide, whereas NGF binding to TrkA, the hih-affity NGFR, enhanced it. These results suggest a possible link between 3-amybid peptide toxicity and preferential degeneration of cells expressing p75NGFR ergic complex in the mammalian brain, the pedunculopontine and laterodorsal tegmental nuclei, neither express p75NGFR nor undergo degeneration in Alzheimer disease (14,15). p75NGFR expression has been demonstrated to enhance apoptosis in the unbound state, whereas, when p75NGFR is bound by nerve growth factor (NGF) or monoclonal antibody, cell survival is enhanced (16). Thus the effect of p75NGFR on neural cells may be analogous to that of CD40, another member of the tumor necrosis factor receptor superfamily, on centrocytes (17).Therefore, the effect of p75NGFR expression on SAP neurotoxicity was evaluated. We report that the expression of p75NGFR decreases the median lethal dose of (3AP on PC12 cell mutants by approximately one order ofmagnitude. These results suggest a possible link between SAP toxicity and preferential degeneration of cells expressing p75NGFR.

Neurotrophin p75 Receptor Is Involved in Neuronal Damage by Prion Peptide-(106–126)

“…NTR (17)(18)(19). The data herein presented support the view that the prion peptide-mediated cell damage occurs through its interaction with the p75 neurotrophin receptor.…”

Elimination of the Class A Scavenger Receptor Does Not Affect Amyloid Plaque Formation or Neurodegeneration in Transgenic Mice Expressing Human Amyloid Protein Precursors

“…43 The LDL receptor-related protein (LRP), like the SR, is a lipoprotein receptor with broad ligand specificity. It binds apolipoprotein E-enriched lipoproteins and functions as a receptor for the proteinase inhibitors Nexin II (␣-secreted hAPP751) and ␣ 2 -macroglobulin.…”

Tumour necrosis factor‐alpha‐ vs. growth factor deprivation‐promoted cell death: distinct converging pathways

“…Like TNF α acting through TNFR, the outcome of NGF acting through p75NTR appears to be cell typeand developmental stage-dependent (Kassis et al ., 1996). In addition, there is evidence to suggest that p75NTR may signal the initiation of apoptosis when in the absence of NGF (Rabizadeh et al ., 1993;Rabizadeh et al ., 1994).…”