title: Defective protein kinase C alpha leads to impaired secretion of soluble beta-amyloid precursor protein from Alzheimer's disease fibroblasts.
abstract: The present study shows that cultured fibroblasts from sporadic AD patients present: a) reduced (-30%) cytosolic protein kinase C (PKC) activity; b) increased KD of phorbol ester binding (+94%) in cytosolic fractions; c) reduced (-30%) soluble protein kinase C alpha immunoreactivity; d) lower (-27.5%) basal soluble APP secretion and e) reduced soluble APP secretion in response to low phorbol ester concentrations (over threefold difference using 9 nM phorbol-12,13-dibutyrate-PdBu). Since the PKC-stimulated secretion of APP leads to the cleavage of the precursor within the amyloidogenic beta-A4 fragment, the reduced PKC activity in AD patients may lead to accumulation of potentially amyloidogenic or toxic APP fragments. A defect in the secretion of soluble amyloid beta-protein precursor is indeed suggested by literature data on familial AD fibroblasts as well as by the reported results.
authors.affiliation: Institute of Pharmacology, University of Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Govoni
authors.forename: M
authors.initials: M
authors.lastname: Racchi
authors.forename: S
authors.initials: S
authors.lastname: Bergamaschi
authors.forename: M
authors.initials: M
authors.lastname: Trabucchi
authors.forename: F
authors.initials: F
authors.lastname: Battaini
authors.forename: A
authors.initials: A
authors.lastname: Bianchetti
authors.forename: G
authors.initials: G
authors.lastname: Binetti
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012016:Reference Values; D012995:Solubility
chemical_list: D016564:Amyloid beta-Protein Precursor; D011493:Protein Kinase C