Document type
Journal articles
Document subtype
Full paper
Title
Evidence for synergistic action of transthyretin and IGF-I over the IGF-I receptor
Participants in the publication
Marta Vieira (Author)
Sónia S. Leal (Author)
Cláudio M. Gomes (Author)
Dep. Química e Bioquímica
BioISI
Maria João Saraiva (Author)
Summary
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 744nM. In summary, our results point to a new TTR role through the IGF-I axis, mediated through TTR-IGF-IR interactions.
Date of Publication
2016-04-00
Institution
BioISI - Biosystems & Integrative Sciences Institute
Where published
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publication Identifiers
ISSN - 0925-4439
Publisher
Elsevier BV
Starting page
797
Last page
804
Document Identifiers
DOI -
https://doi.org/10.1016/j.bbadis.2016.01.008
URL -
http://dx.doi.org/10.1016/j.bbadis.2016.01.008
Rankings
SCIMAGO Q1 (2016) - 2.593 - Molecular Medicine
Web Of Science Q1 (2017) - 5.108 - BIOCHEMISTRY & MOLECULAR BIOLOGY - SCIE
SCOPUS Q1 (2015) - 2.8 - Molecular Medicine
Keywords
Glutamate
Ischemia
Protein–protein interaction