Defective Protein Kinase C α Leads to Impaired Secretion of Soluble β‐Amyloid Precursor Protein from Alzheimer's Disease Fibroblastsa
- 1 January 1996
- journal article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 777 (1) , 332-337
- https://doi.org/10.1111/j.1749-6632.1996.tb34442.x
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 resultsKeywords
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