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.

Govoni, S., Racchi, M., Bergamaschi, S., Trabucchi, M.m., Battaini, F.m., Bianchetti, A., et al. (1996). Defective protein kinase C alpha leads to impaired secretion of soluble beta-amyloid precursor protein from Alzheimer's disease fibroblasts. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 777, 332-337 [DOI: 10.1111/j.1749-6632.1996.tb34442.x].

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

TRABUCCHI, MARCO MARIO;BATTAINI, FIORENZO MARIA;
1996-01-17

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.
17-gen-1996
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
protein kinase C; solubility; cell line; phosphorylation; cytosol; amyloid beta-protein precursor; alzheimer disease; reference values; fibroblasts; humans
Govoni, S., Racchi, M., Bergamaschi, S., Trabucchi, M.m., Battaini, F.m., Bianchetti, A., et al. (1996). Defective protein kinase C alpha leads to impaired secretion of soluble beta-amyloid precursor protein from Alzheimer's disease fibroblasts. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 777, 332-337 [DOI: 10.1111/j.1749-6632.1996.tb34442.x].
Govoni, S; Racchi, M; Bergamaschi, S; Trabucchi, Mm; Battaini, Fm; Bianchetti, A; Binetti, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/8926
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