Yankner B A, Duffy L K, Kirschner D A
Department of Neurology, Harvard Medical School, Boston, MA 02115.
Science. 1990 Oct 12;250(4978):279-82. doi: 10.1126/science.2218531.
The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid beta protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid beta protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.
β-淀粉样蛋白沉积于阿尔茨海默病患者的大脑中，但其致病作用尚不清楚。在培养实验中，低浓度的β-淀粉样蛋白对未分化的海马神经元具有神经营养作用，而高浓度时则对成熟神经元具有神经毒性。在分化的神经元中，β-淀粉样蛋白会导致树突和轴突回缩，随后神经元死亡。一部分β-淀粉样蛋白（氨基酸25至35）介导了营养和毒性作用，并且与速激肽神经肽家族同源。速激肽拮抗剂可模拟β-淀粉样蛋白的作用，而特异性速激肽激动剂则可完全逆转其作用。因此，β-淀粉样蛋白可作为分化神经元的神经营养因子，但在成熟神经元中浓度过高时，如在阿尔茨海默病中，可能会导致神经元变性。
