Transthyretin inhibition of amyloid beta aggregation and toxicity

Clin Biochem. 2005 Dec;38(12):1112-9. doi: 10.1016/j.clinbiochem.2005.08.007. Epub 2005 Sep 22.

Abstract

Objectives: The aim of this study was to investigate transthyretin (prealbumin) effects on Abeta25-35-induced cytotoxicity.

Design and methods: In view of the well-recognized literature data demonstrating that Abeta25-35 fibrillar aggregates cause in vitro cytotoxicity to human red blood cells and apoptotic changes to SK-N-BE neuroblastoma cells in cultures (ultrastructural evidence), we tested transthyretin effects on these two experimental models.

Results: Incubation of Abeta25-35 with transthyretin (at transthyretin concentrations equal to CSF physiological levels) demonstrated both inhibition of red blood cells lysis and neutralization of SK-N-BE neuroblastoma cells ultrastructural apoptotic changes. Moreover, transthyretin was shown to be able to inhibit the formation of fibrillar macroaggregates of Abeta25-35.

Conclusions: The findings imply that experimental systems investigating Abeta-induced cytotoxicity consider the protective interaction of transthyretin with Abeta; an interaction to be considered also in vivo in view of the fact that transthyretin immunoreactivity has been previously demonstrated in amyloid plaques of brains from Alzheimer's disease patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Congo Red / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Erythrocytes / drug effects*
  • Hemolysis / drug effects
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity
  • Prealbumin / analysis
  • Prealbumin / pharmacology*
  • Sensitivity and Specificity
  • Spectrophotometry / methods
  • Tumor Cells, Cultured

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Prealbumin
  • amyloid beta-protein (25-35)
  • Congo Red