Defective protein kinase C α leads to impaired secretion of soluble β-amyloid precursor protein from Alzheimer's disease fibroblasts

S. Govoni, M. Racchi, S. Bergamaschi, M. Trabucchi, F. Battaini, A. Bianchetti, G. Binetti

Research output: Contribution to journalArticle

Abstract

The present study shows that cultured fibroblasts from sporadic AD patients present: a) reduced (-30%) cytosolic protein kinase C (PKC) activity; b) increased K(D) of phorbol ester binding (+94%) in cytosolic fractions; c) reduced (-30%) soluble protein kinase Cα 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 β-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 β-protein precursor is indeed suggested by literature data on familial AD fibroblasts as well as by the reported results.

Original languageEnglish
Pages (from-to)332-337
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume777
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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