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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Vieira, M (Autor) Outra; Leal, SS (Autor) Outra; Gomes, CM (Autor) Outra; Maria Joao Saraiva (Autor) FCUP

Revista

Título: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1862

Páginas: 797-804

ISSN: 0925-4439

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 4 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8