NEUROTROPHIC AND NEUROTOXIC EFFECTS OF AMYLOID BETA-PROTEIN - REVERSAL BY TACHYKININ NEUROPEPTIDES
NEUROTROPHIC AND NEUROTOXIC EFFECTS OF AMYLOID BETA-PROTEIN - REVERSAL BY TACHYKININ NEUROPEPTIDES
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DOI：
10.1126/science.2218531
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发表时间：
1990-10-12
期刊：
影响因子：
56.9
通讯作者：
KIRSCHNER, DA
中科院分区：
文献类型：
--
作者：
YANKNER, BA;DUFFY, LK;KIRSCHNER, DA
淀粉样蛋白。β。蛋白质沉积在阿尔茨海默病患者的大脑中，但其致病作用尚不清楚。在培养中，淀粉样蛋白。β。低浓度的蛋白质对未分化的海马神经元有神经营养作用，高浓度的蛋白质对成熟神经元有神经毒性作用。在分化的神经元中，淀粉样β蛋白。蛋白质导致树突和轴突回缩，随后神经元死亡。淀粉样蛋白的一部分。蛋白质(25-35个氨基酸)介导营养和毒性效应，并与速激肽神经肽家族同源。淀粉样β蛋白的影响。蛋白质被速激肽拮抗剂模仿，并被特定的速激肽激动剂完全逆转。因此，淀粉样蛋白.β。蛋白质可以作为神经营养因子来分化神经元，但在成熟神经元中，蛋白质的浓度过高，如阿尔茨海默病的S病，可能会导致神经元退化。
The amyloid .beta. protein is deposited in the brains of patients with Alzheimer''s disease but its pathogeneic 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.