Dm. Muller et al., MUSCARINIC M1 RECEPTOR AGONISTS INCREASE THE SECRETION OF THE AMYLOIDPRECURSOR PROTEIN ECTODOMAIN, Life sciences, 60(13-14), 1997, pp. 985-991
Citations number
35
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Amyloid deposits in Alzheimer's disease are composed of amyloid beta-p
eptides (A beta) that are derived from the larger amyloid precursor pr
otein (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 d
omain, followed by the release of the soluble APP ectodomain (APPs). I
n this study, we show that the m1-selective agonist talsaclidine conce
ntration-dependently increased APPs release from both transfected huma
n astrocytoma cell lines and rat brain slices. This increase was block
ed by atropine. In contrast, the M2 antagonist BIBN 99 failed to incre
ase APPs release, and decreased it at higher concentrations. These res
ults show that talsaclidine can effectively modulate alpha-secretase p
rocessing of APP in human cell lines and in brain tissue. The data sug
gest that talsaclidine may be a useful candidate drug to modulate APP
processing in Alzheimer's disease.