Evidence for synergistic action of transthyretin and IGF-I over the IGF-I receptor

Marta Vieira, Sonia Cristina Solano, Claudio Emanuel Gomes, Maria João Saraiva

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Transthyretin (TTR) has a neuroprotective role in the central nervous system (CNS) in Alzheimer's disease (AD) and cerebral ischemia. Increased levels of TTR and activated insulin-like growth factor I receptor (IGF-IR) are associated with reduced neurodegeneration in an AD mouse model. In the present study, we found that TTR and IGF-I have a synergistic effect on activation of one of the IGF-IR signaling pathways. Hippocampus of TTR null mice present decreased levels of phosphorylated IGF-IR and Akt when compared with TTR wild type littermate animals. Cell studies reveal the synergistic effect of TTR and IGF-I in promoting IGF-IR signaling even under glutamate induced toxicity. TTR:IGF-IR complexes are identified and a bio-layer interferometry assay demonstrated an interaction between TTR and IGF-IR with a KD ranging from 99 to 744 nM. In summary, our results point to a new TTR role through the IGF-I axis, mediated through TTR-IGF-IR interactions.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalBiochimica Et Biophysica Acta-Molecular Basis Of Disease
Volume1862
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016

Keywords

  • Glutamate
  • Ischemia
  • Protein-protein interaction
  • Synergy

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