First Author | Vieira M | Year | 2016 |
Journal | Biochim Biophys Acta | Volume | 1862 |
Issue | 4 | Pages | 797-804 |
PubMed ID | 26804653 | Mgi Jnum | J:256745 |
Mgi Id | MGI:6105425 | Doi | 10.1016/j.bbadis.2016.01.008 |
Citation | Vieira M, et al. (2016) Evidence for synergistic action of transthyretin and IGF-I over the IGF-I receptor. Biochim Biophys Acta 1862(4):797-804 |
abstractText | 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. |