In vitro effects of metrifonate on neuronal amyloid precursor protein processing and protein kinase C level

Magdolna Pakaski, Zoltan Rakonczay, Ida Fakla, Henrietta Papp, Peter Kasa

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Alteration in the processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease (AD). It has been suggested that acetylcholinesterase (AChE) inhibitors, which promote the cholinergic function and consequently improve the cognitive deficits, may also exert a neuroprotective effect by activating normal APP processing. We now report that an irreversible AChE inhibitor (metrifonate) increase the cell-associated APP level in a basal forebrain neuronal culture and also elevate the amount of APP secreted into the medium. The alterations in APP processing were accompanied by increased protein kinase C (PKC) levels. The results suggest that AChE inhibitors modulate the metabolism of APP, possibly via their stimulatory effects on PKC. Since changes in the activity and level of PKC may be involved in the pathogenesis of AD, it is concluded that the beneficial effect of metrifonate in AD therapy may be due not only to the stimulatory cholinergic function, but also to its activating effect on PKC.

Original languageEnglish
Pages (from-to)266-270
Number of pages5
JournalBrain research
Volume863
Issue number1-2
DOIs
Publication statusPublished - Apr 28 2000

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Keywords

  • APP
  • Alzheimer's disease
  • Immunoblotting
  • Neuronal culture
  • PKC

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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