Release of Alzheimer Amyloid Precursor Derivatives Stimulated by Activation of Muscarinic Acetylcholine Receptors
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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Muscarinic M1 acetylcholine receptors elevate cleavage of APP by α-secretase, which lowers Aβ production and levels.
“Similarly, muscarinic M1 acetylcholine receptors elevate cleavage of APP by α-secretase, which lowers Aβ production and levels (8, 9)”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [9]
M1-mediated down-regulation of Aβ acts by increasing α-secretase cleavage of APP.
“Similar to our current data with serotonin, M1-mediated down-regulation of Aβ acts by increasing α-secretase cleavage of APP (8, 9).”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [9]
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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)
- ORCID
- Slack, Barbara E.
- 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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