Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis - A possible mechanism for Alzheimer's disease
Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis - A possible mechanism for Alzheimer's disease
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DOI：
10.1172/jci119772
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发表时间：
1997-11-01
影响因子：
15.9
通讯作者：
Gilchrest, BA
中科院分区：
文献类型：
--
作者：
Yaar, M;Zhai, S;Gilchrest, BA
阿尔茨海默氏病是一种神经退行性疾病，其特征在于聚集的β-淀粉样肽在脑中的细胞外沉积，推测其起致病作用，以及表达75-kD神经营养因子受体（p75（NTR））的神经元的优先损失。利用大鼠皮层神经元和稳定表达p75（NTR）的NIH-3 T3细胞系，我们发现β-淀粉样肽特异性结合p75（NTR）。此外，表达p75（NTR）的3 T3细胞，而不是缺乏受体的野生型对照细胞，在聚集的β-淀粉样蛋白存在下经历凋亡。表达生理水平p75（NTR）的正常神经嵴衍生的黑素细胞在聚集的β-淀粉样蛋白存在下发生凋亡，但在反向合成的对照肽存在下不发生凋亡。这些数据意味着阿尔茨海默病中的神经元死亡至少部分是由β-淀粉样蛋白与p75（NTR）的相互作用介导的，并提出了治疗干预的新靶点。
Alzheimer's disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of aggregated beta-amyloid peptide, presumed to play a pathogenic role, and by preferential loss of neurons that express the 75-kD neurotrophin receptor (p75(NTR)). Using rat cortical neurons and NIH-3T3 cell line engineered to stably express p75(NTR), we find that the beta-amyloid peptide specifically binds the p75(NTR). Furthermore, 3T3 cells expressing p75(NTR), but not wild-type control cells lacking the receptor, undergo apoptosis in the presence of aggregated beta-amyloid. Normal neural crest-derived melanocytes that express physiologic levels of p75(NTR) undergo apoptosis in the presence of aggregated beta-amyloid, but not in the presence of control peptide synthesized in reverse. These data imply that neuronal death in Alzheimer's disease is mediated, at least in part, by the interaction of beta-amyloid with p75(NTR), and suggest new targets for therapeutic intervention.