Nerve growth factor potentiates the neurotoxicity of beta amyloid.
Nerve growth factor potentiates the neurotoxicity of beta amyloid.
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DOI：
10.1073/pnas.87.22.9020
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发表时间：
1990-11
影响因子：
11.1
通讯作者：
B. Yankner;Alfredo Cáceres;Lawrence K. Duffy
中科院分区：
文献类型：
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作者：
B. Yankner;Alfredo Cáceres;Lawrence K. Duffy
生长因子在阿尔茨海默病发病机制中的作用尚不清楚。β-淀粉样蛋白在阿尔茨海默病的大脑中异常积累，并且对培养的分化的海马神经元具有神经毒性。神经生长因子（NGF）使β-淀粉样蛋白多肽的神经毒性效力增加约100，000倍，这导致β-淀粉样蛋白神经毒性EC 50从0.1 μ M降低至1 pM。这种增强作用的神经生长因子被逆转的单克隆抗体对神经生长因子，并没有观察到各种其他神经营养生长因子。海马神经元暴露于非常低浓度的β淀粉样蛋白单独导致免疫反应性神经生长因子受体的显着诱导。添加NGF和β淀粉样蛋白导致NGF受体阳性神经元出现神经退行性变化。阿尔茨海默病中海马和基底前脑胆碱能神经元的早期和深度变性可能是β淀粉样蛋白与NGF的神经毒性相互作用的结果。
The role of growth factors in the pathogenesis of Alzheimer disease is unknown. The beta-amyloid protein accumulates abnormally in the brain in Alzheimer disease and is neurotoxic to differentiated hippocampal neurons in culture. Nerve growth factor (NGF) increased the neurotoxic potency of a beta-amyloid polypeptide by a factor of approximately 100,000, which resulted in a reduction of the beta-amyloid neurotoxic EC50 from 0.1 microM to 1 pM. This potentiating effect of NGF was reversed by a monoclonal antibody against NGF and was not observed for a variety of other neurotrophic growth factors. Exposure of hippocampal neurons to very low concentrations of beta amyloid alone resulted in a marked induction of immunoreactive NGF receptors. Addition of NGF with beta amyloid resulted in the appearance of neurodegenerative changes in NGF receptor-positive neurons. The early and profound degeneration of hippocampal and basal forebrain cholinergic neurons that occurs in Alzheimer disease may result from a neurotoxic interaction of beta amyloid with NGF.