NEUROTOXICITY OF A FRAGMENT OF THE AMYLOID PRECURSOR ASSOCIATED WITH ALZHEIMERS-DISEASE
NEUROTOXICITY OF A FRAGMENT OF THE AMYLOID PRECURSOR ASSOCIATED WITH ALZHEIMERS-DISEASE
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DOI：
10.1126/science.2474201
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发表时间：
1989-07-28
期刊：
影响因子：
56.9
通讯作者：
NEVE, RL
中科院分区：
文献类型：
--
作者：
YANKNER, BA;DAWES, LR;NEVE, RL
老年斑和脑血管中的淀粉样蛋白沉积是阿尔茨海默病的标志。淀粉样蛋白本身是否有助于神经退行性过程，或者仅仅是该过程的副产品尚不清楚。用人淀粉样前体蛋白基因的部分转染嗜铬细胞瘤（PC12）和成纤维细胞（NIH 3T3）细胞系。当用神经生长因子诱导分化成神经元细胞时，表达前体蛋白的特定含淀粉样蛋白片段的稳定PC12细胞转染子逐渐退化。这些细胞的条件培养基对原代海马培养物中的神经元有毒性，并且毒性剂可以通过针对淀粉样蛋白多肽的抗体的免疫吸收来去除。因此，衍生自淀粉样蛋白前体的肽可能是神经毒性的。
Amyloid deposition in senile plaques and the cerebral vasculature is a marker of Alzheimer''s Disease. Whether amyloid itself contributes to the neurodegenerative process or is simply a by-product of that process is unknown. Phenochromocytoma (PC12) and fibroblast (NIH 3T3) cell lines were transfected with portions of the gene for the human amyloid precursor protein. Stable PC12 cell transfectants expressing a specific amyloid-containing fragment of the precursor protein gradually degenerated when induced to differentiate into neuronal cells with nerve growth factor. Conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against the amyloid polypeptide. Thus, a peptide derived from the amyloid precursor may be neurotoxic.