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Defective Protein Kinase C α Leads to Impaired Secretion of Soluble β‐Amyloid Precursor Protein from Alzheimer's Disease Fibroblasts a
Author(s) -
GOVONI S.,
RACCHI M.,
BERGAMASCHI S.,
TRABUCCHI M.,
BATTAINI F.,
BIANCHETTI A.,
BINETTI G.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb34442.x
Subject(s) - protein kinase c , secretion , cytosol , amyloid precursor protein , phorbol , p3 peptide , phorbol ester , chemistry , protein kinase a , kinase , microbiology and biotechnology , endocrinology , alzheimer's disease , biochemistry , medicine , biology , enzyme , disease
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.