Antibody-Regulated Neurotoxic Function of Cell-Surface β-Amyloid Precursor Protein
Antibody-Regulated Neurotoxic Function of Cell-Surface β-Amyloid Precursor Protein
复制标题
DOI：
10.1006/mcne.2000.0910
复制
发表时间：
2000-12
影响因子：
3.5
通讯作者：
H. Sudo;Hong Jiang;T. Yasukawa;Y. Hashimoto;T. Niikura;M. Kawasumi;Shuji Matsuda;Y. Takeuchi
中科院分区：
文献类型：
--
作者：
H. Sudo;Hong Jiang;T. Yasukawa;Y. Hashimoto;T. Niikura;M. Kawasumi;Shuji Matsuda;Y. Takeuchi
APP是β-淀粉样蛋白的跨膜前体，其突变导致早发性家族性阿尔茨海默病。我们报告了正常野生型 APP (wtAPP) 的毒性功能。用抗 APP 抗体过表达 wtAPP，对神经元 F11 细胞、永生化胚胎第 13 天神经元进行处理，导致死亡。亲本 F11 细胞中的抗体不诱导死亡。抗体引起的死亡通过细胞表面APP而不是通过分泌的APP以百日咳毒素敏感的方式发生，并且是典型的细胞凋亡，在过表达wtAPP的原代星形胶质细胞或神经胶质瘤细胞中未观察到，但在原代皮质神经元中观察到。因此，细胞表面 APP 作为神经元死亡的细胞外可控调节剂发挥着毒性功能。这项研究为细胞表面 wtAPP 的正常和病理功能提供了新的见解。
APP is a transmembrane precursor of beta-amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of normal wild-type APP (wtAPP). Treatment of neuronal F11 cells, immortalized embryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies caused death. Death was not induced by antibody in parental F11 cells. Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in primary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study provides a novel insight into the normal and pathological functions of cell-surface wtAPP.