Searching across hundreds of databases
Diabetes and impaired brain insulin signaling are linked to the pathogenesis of Alzheimer's disease (AD). The association between diabetes and AD-associated amyloid pathology is stronger among carriers of the apolipoprotein E (APOE) ε4 gene allele, the strongest genetic risk factor for late-onset AD. Here we report that apoE4 impairs neuronal insulin signaling in human apoE-targeted replacement (TR) mice in an age-dependent manner. High-fat diet (HFD) accelerates these effects in apoE4-TR mice at middle age. In primary neurons, apoE4 interacts with insulin receptor and impairs its trafficking by trapping it in the endosomes, leading to impaired insulin signaling and insulin-stimulated mitochondrial respiration and glycolysis. In aging brains, the increased apoE4 aggregation and compromised endosomal function further exacerbate the inhibitory effects of apoE4 on insulin signaling and related functions. Together, our study provides novel mechanistic insights into the pathogenic mechanisms of apoE4 and insulin resistance in AD.
Pubmed ID: 28957663 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets INSR
View all literature mentionsThis polyclonal targets NR2B
View all literature mentionsThis monoclonal targets Rab5 antibody [EPR5438]
View all literature mentionsThis monoclonal targets Phospho-Insulin Receptor beta (Tyr1345)
View all literature mentionsThis polyclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Human Insulin R / CD220
View all literature mentionsThis monoclonal targets Human Insulin R/CD220 ylated MAb (Clone 243524)
View all literature mentionsThis monoclonal targets GSK-3beta (27C10) Rabbit mAb
View all literature mentionsThis polyclonal targets Apolipoprotein E
View all literature mentionsThis monoclonal targets Insulin Receptor (beta-Subunit) clone CT-3
View all literature mentionsThis monoclonal targets Glutamate Receptor 2 extracellular clone 6C4
View all literature mentionsThis monoclonal targets alpha 1 Sodium Potassium ATPase antibody [464.6] - Plasma Membrane Marker
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line SH-SY5Y is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name B6:129S5-Retnlbtm1Lex from IMSR.
View all literature mentionsMus musculus with name B6:129S5-TomtGt(OST184065)Lex from IMSR.
View all literature mentionsCell line Huh-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
