Rabizadeh S, Bitler C M, Butcher L L, Bredesen D E
Department of Neurology, University of California, Los Angeles 90024.
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10703-6. doi: 10.1073/pnas.91.22.10703.
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.
低亲和力神经生长因子受体（NGFR）p75NGFR在未结合神经生长因子（NGF）时诱导细胞凋亡，但在与NGF结合时增强神经细胞存活。基底前脑胆碱能神经元在成人大脑中表达最高水平的p75NGFR，且优先参与阿尔茨海默病，这就提出了一个问题，即p75NGFR的表达与阿尔茨海默病中基底前脑胆碱能神经元变性之间是否可能存在功能关系。野生型和突变型PC12细胞表达p75NGFR可增强β-淀粉样肽诱导的细胞死亡。NGF与p75NGFR结合可抑制β-淀粉样肽的毒性，而NGF与高亲和力NGFR TrkA结合则增强其毒性。这些结果表明β-淀粉样肽毒性与表达p75NGFR的细胞优先变性之间可能存在联系。
