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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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

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Tacrine
Amyloid beta-Protein Precursor
Cultured Cells
Serum Amyloid A Protein
Secretory Pathway
Cholinesterase Inhibitors
Membrane Glycoproteins
Conditioned Culture Medium
Pharmaceutical Preparations
Alzheimer Disease
Protein Isoforms
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reversibility of the effect of tacrine on the secretion of the β-amyloid precursor protein in cultured cells. / Lahiri, Debomoy.

In: Neuroscience Letters, Vol. 181, No. 1-2, 07.11.1994, p. 149-152.

Research output: Contribution to journalArticle

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