Open AccessCholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor.
Author(s) -
Joseph D. Buxbaum,
M. Oishi,
Henry I. Chen,
Ronit PinkasKramarski,
Eric Jaffe,
Samuel Gandy,
Paul Greengard
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.21.10075
Subject(s) - amyloid precursor protein , protein kinase c , secretion , cholinergic , amyloid precursor protein secretase , protein kinase a , biology , p3 peptide , beta (programming language) , endocrinology , chemistry , medicine , alzheimer's disease , microbiology and biotechnology , signal transduction , kinase , disease , computer science , programming language
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.