Cited by 898Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Release of Alzheimer Amyloid Precursor Derivatives Stimulated by Activation of Muscarinic Acetylcholine Receptors

Nitsch, Roger M., Slack, Barbara E., Wurtman, Richard J., Growdon, John H.·1992·Science

Abstract

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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Crossref · 10.1126/science.1411529

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Authors
Nitsch, R. M., Slack, B. E., Wurtman, R. J., & Growdon, J. H.
Affiliations
  • Harvard University (US)
  • Massachusetts Institute of Technology (US)
Venue
Science
Published
1992-10-09
Volume
258
Issue
5080
Pages
304-307
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1990543766
Cited by
898
References
1
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 12 · 2021: 9 · 2020: 14 · 2019: 9 · 2018: 11 · 2017: 10 · 2016: 13 · 2015: 19 · 2014: 18 · 2013: 26 · 2012: 27
FWCI
27.17
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid precursor protein, Alzheimer's disease, muscarinic receptors, M1 receptor, M3 muscarinic receptor, carbachol, APP processing, protein kinases, staurosporine, neurotransmitter receptors, amyloid deposition
MeSH terms
Alkaloids, Alzheimer Disease, Atropine, Brain Chemistry, Carbachol, Cell Line, Embryo, Mammalian, Humans, Kidney, Kinetics, Protein Kinase C, Receptors, Muscarinic, Transfection, Blotting, Western, Amyloid beta-Protein Precursor, Staurosporine

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