CHOLINERGIC AGONISTS AND INTERLEUKIN-1 REGULATE PROCESSING AND SECRETION OF THE ALZHEIMER BETA/A4 AMYLOID PROTEIN-PRECURSOR
CHOLINERGIC AGONISTS AND INTERLEUKIN-1 REGULATE PROCESSING AND SECRETION OF THE ALZHEIMER BETA/A4 AMYLOID PROTEIN-PRECURSOR
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DOI：
10.1073/pnas.89.21.10075
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
GREENGARD, P
中科院分区：
文献类型：
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作者：
BUXBAUM, JD;OISHI, M;GREENGARD, P
已知磷酸酯激活蛋白激酶C可加速β /A4淀粉样蛋白前体的加工和分泌。我们现在已经研究了各种增加靶细胞蛋白激酶C活性的第一信使，因为它们影响β /A4淀粉样蛋白前体代谢的能力。在阿尔茨海默病中发生改变的乙酰胆碱和白细胞介素1被证明通过分泌裂解途径增加β /A4淀粉样蛋白前体的加工。胆碱能激动剂刺激人胶质瘤和神经母细胞瘤细胞以及转染M1受体的PC12细胞的分泌，而白细胞介素1刺激人内皮细胞和胶质瘤细胞的分泌。
Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer disease, were shown to increase processing of the beta/A4 amyloid protein precursor via the secretory cleavage pathway. Cholinergic agonists stimulated secretion in human glioma and neuroblastoma cells as well as in PC12 cells transfected with the M1 receptor, while interleukin 1 stimulated secretion in human endothelial and glioma cells.