Muscarinic m1 receptor agonists increase the secretion of the amyloid precursor protein ectodomain
| Autor: | Roger Nitsch, Steven A. Farber, Dorothea M. Müller, Klaus Mendla |
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| Rok vydání: | 1997 |
| Předmět: |
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medicine.medical_specialty Pyridines Muscarinic Agonists Talsaclidine General Biochemistry Genetics and Molecular Biology Amyloid beta-Protein Precursor Dibenzazepines Internal medicine Endopeptidases mental disorders Tumor Cells Cultured medicine Amyloid precursor protein Muscarinic acetylcholine receptor M4 Animals Aspartic Acid Endopeptidases Humans General Pharmacology Toxicology and Pharmaceutics Dose-Response Relationship Drug biology Chemistry Receptor Muscarinic M1 P3 peptide Muscarinic acetylcholine receptor M2 General Medicine Muscarinic acetylcholine receptor M1 Receptors Muscarinic Rats Cell biology Endocrinology Alpha secretase Rats Inbred Lew biology.protein Amyloid Precursor Protein Secretases Amyloid precursor protein secretase |
| Zdroj: | Life Sciences. 60:985-991 |
| ISSN: | 0024-3205 |
| Popis: | Amyloid deposits in Alzheimer's disease are composed of amyloid beta-peptides (A beta) that are derived from the larger amyloid precursor protein (APP). Proteolytic APP processing is activity-dependent, and it can be regulated by muscarinic acetylcholine receptors. In particular, muscarinic m1 receptor subtypes increase cleavage within the A beta domain, followed by the release of the soluble APP ectodomain (APPs). In this study, we show that the m1-selective agonist talsaclidine concentration-dependently increased APPs release from both transfected human astrocytoma cell lines and rat brain slices. This increase was blocked by atropine. In contrast, the M2 antagonist BIBN 99 failed to increase APPs release, and decreased it at higher concentrations. These results show that talsaclidine can effectively modulate alpha-secretase processing of APP in human cell lines and in brain tissue. The data suggest that talsaclidine may be a useful candidate drug to modulate APP processing in Alzheimer's disease. |
| Databáze: | OpenAIRE |
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