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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Vieira, M (Author) Other; Leal, SS (Author) Other; Gomes, CM (Author) Other; Maria Joao Saraiva (Author) FCUP

Journal

Title: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1862

Pages: 797-804

ISSN: 0925-4439

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00K-6MT

DOI: 10.1016/j.bbadis.2016.01.008

Abstract (EN): 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 K-D 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8