Transthyretin inhibition of amyloid beta aggregation and toxicity.

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.

• Authors: S Giunta, M B Valli, R Galeazzi, P Fattoretti, E H Corder, L Galeazzi
• Journal: Clinical biochemistry (Clin Biochem) Vol. 38 Issue 12 Pg. 1112-9 (Dec 2005) ISSN: 0009-9120 [Print] United States
• PMID: 16183049 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Amino Acid Sequence
• Amyloid beta-Peptides (antagonists & inhibitors, metabolism, 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, pathology)
• Peptide Fragments (antagonists & inhibitors, metabolism, toxicity)
• Prealbumin (analysis, pharmacology)
• Sensitivity and Specificity
• Spectrophotometry (methods)
• Tumor Cells, Cultured