EXPRESSION OF THE LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR ENHANCES BETA-AMYLOID PEPTIDE TOXICITY
EXPRESSION OF THE LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR ENHANCES BETA-AMYLOID PEPTIDE TOXICITY
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DOI：
10.1073/pnas.91.22.10703
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发表时间：
1994-10-25
影响因子：
11.1
通讯作者：
BREDESEN, DE
中科院分区：
文献类型：
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作者：
RABIZADEH, S;BITLER, CM;BREDESEN, DE
低亲和性神经生长因子受体（NGFR） p75（NGFR）在没有神经生长因子（NGF）结合的情况下诱导细胞凋亡，而在与NGF结合的情况下增强神经存活。基底前脑胆碱能神经元在成人大脑中表达最高水平的p75(NGFR)，并优先参与阿尔茨海默病，这就提出了p75（NGFR）的表达与阿尔茨海默病基底前脑胆碱能神经元变性之间是否存在功能关系的问题。野生型和突变型PC12细胞表达p75（NGFR）可增强β -淀粉样肽诱导的细胞死亡。NGF与p75（NGFR）结合可抑制β -淀粉样肽的毒性，而与高亲和NGFR TrkA结合可增强其毒性。这些结果表明β -淀粉样肽毒性与表达p75（NGFR）的细胞的优先变性之间可能存在联系。
The low-affinity nerve growth factor receptor (NGFR) p75(NGFR) 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 p75(NGFR) 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 p75(NGFR) and basal forebrain cholinergic neuronal degeneration in Alzheimer disease. The expression of p75(NGFR) by wild-type and mutant PC12 cells potentiated cell death induced by beta-amyloid peptide. NGF binding to p75(NGFR) 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 p75(NGFR).