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Science 9 October 1992:
Vol. 258. no. 5080, pp. 304 - 307
DOI: 10.1126/science.1411529
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Articles

Science, Vol 258, Issue 5080, 304-307
Copyright © 1992 by American Association for the Advancement of Science

articles

Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors

RM Nitsch, BE Slack, RJ Wurtman, and JH Growdon

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.

Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor-activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing.


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Arch Neurol 54, 465-473
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Amyloid beta -Protein and the Genetics of Alzheimer's Disease.
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Serotonin 5-HT2a and 5-HT2c Receptors Stimulate Amyloid Precursor Protein Ectodomain Secretion.
R. M. Nitsch, M. Deng, J. H. Growdon, and R. J. Wurtman (1996)
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Phosphorylation of the Cytosolic Domain of Peptidylglycine alpha-Amidating Monooxygenase.
H.-Y. Yun, S. L. Milgram, H. T. Keutmann, and B. A. Eipper (1995)
J. Biol. Chem. 270, 30075-30083
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Tyrosine Phosphorylation-dependent Stimulation of Amyloid Precursor Protein Secretion by the m3 Muscarinic Acetylcholine Receptor.
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Extracellular Matrix Influences the Biogenesis of Amyloid Precursor Protein in Microglial Cells.
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Muscarinic Regulation of Alzheimer's Disease Amyloid Precursor Protein Secretion and Amyloid beta-Protein Production in Human Neuronal NT2N Cells.
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N. R. Cutler, J. J. Sramek, R. Levy, S. I. Gracon, M. Lachs, K. Meloff, K. L. Davis, L. J. Thal, and J. H. Growdon (1993)
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