Reversibility of the effect of tacrine on the secretion of the β-amyloid precursor protein in cultured cells

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21 Scopus citations

Abstract

The amyloid β-protein (Aβ) of Alzheimer's disease is derived from a family of large integral membrane glycoproteins, β-amyloid precursor proteins (βAPP). Two secretory proteolytic pathways are involved in the metabolism of βAPP. The major pathway involves cleavage within the Aβ sequence and generates carboxyl-truncated derivatives of βAPP which are secreted into the conditioned medium of cells. The minor 'amyloidogenic' pathway results in the production of Aβ. Here, cell cultures were used to examine the metabolism of βAPP by tacrine, a centrally active cholinesterase inhibitor reported to improve cognitive deficits. Treatment with tacrine in cells resulted in the drastic inhibition of secretion of the major isoforms of βAPP into the medium. The effect of tacrine can be reversed by washing away the drug from the cells. Treatment with tacrine did not change the level of either HSP-70 or LDH. Thus, the inhibitory effect of tacrine on the secretion of βAPP was not due to the permanent damage or loss of cells as normal release of βAPP could be restored when the drug was washed away.

Original languageEnglish (US)
Pages (from-to)149-152
Number of pages4
JournalNeuroscience Letters
Volume181
Issue number1-2
DOIs
StatePublished - Nov 7 1994

Keywords

  • Acetylcholinesterase inhibitor
  • Alzheimer's disease
  • Kunitz-protease inhibitor domain
  • Neuroblastoma cell
  • PC12 cell
  • Tacrine
  • βAPP secretion

ASJC Scopus subject areas

  • Neuroscience(all)

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