AI Article Synopsis
- A complementary DNA encoding a mutant form of human beta-amyloid precursor protein related to familial Alzheimer's disease was cloned into a mammalian expression vector and transfected into CHO cells to study its effects.
- The researchers tested the impact of two muscarinic receptor agonists, xanomeline and carbachol, on the release of soluble APP and beta-amyloid peptide from these cells.
- Xanomeline was found to be significantly more effective than carbachol in stimulating APP release, and both compounds reduced beta-amyloid peptide secretion, suggesting potential benefits for cholinergic therapy in Alzheimer's treatment.
Article Abstract
Complementary DNA (cDNA) encoding human beta-amyloid precursor protein familial Alzheimer's disease (FAD) Swedish mutant (beta APPSM) form was cloned into a mammalian expression vector (PK255) containing the CMV promoter. The vector was transfected into Chinese hamster ovary cells containing human muscarinic m1 receptors (CHO-m1), and clonal cells stably expressing beta APPSM were isolated. The effects of m1-receptor activation by the selective m1 agonist xanomeline and the non-selective muscarinic agonist carbachol on processing of beta APPSM to release soluble APP (APPs) and beta-amyloid peptide (A beta) were compared. Xanomeline stimulated APP release with a potency 1000-fold greater than that observed for carbachol. Concentrations of carbachol and xanomeline producing maximal effects on APPs release reduced the secretion of A beta by 28 and 46%, respectively. These results extend previous studies with xanomeline and suggest that cholinergic replacement therapy for Alzheimer's disease may reduce amyloid deposition.
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| http://dx.doi.org/10.1006/bbrc.1998.8235 | DOI Listing |
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Effects of the M1 agonist xanomeline on processing of human beta-amyloid precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1 cells.
Biochem Biophys Res Commun
March 1998
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Article Synopsis
- A complementary DNA encoding a mutant form of human beta-amyloid precursor protein related to familial Alzheimer's disease was cloned into a mammalian expression vector and transfected into CHO cells to study its effects.
- The researchers tested the impact of two muscarinic receptor agonists, xanomeline and carbachol, on the release of soluble APP and beta-amyloid peptide from these cells.
- Xanomeline was found to be significantly more effective than carbachol in stimulating APP release, and both compounds reduced beta-amyloid peptide secretion, suggesting potential benefits for cholinergic therapy in Alzheimer's treatment.
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