Insulin–likegrowthfactor2 (IGF2) protects against Huntington’s disease through the extracellular disposal of protein aggregates
by Kayla
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Impaired neuronal proteostasis is a prominent feature of many neurodegenerative diseases, highlighting the changes in the functioning of the endoplasmic reticulum (ER). We previously reported that targets the transcription factor XBP1, a key mediator of ER stress response, delay progression of the disease and reduce aggregation of the protein in a variety of models of neurodegeneration.
To identify modifiers of disease genes that may explain the neuroprotective effects XBP1 deficiency, we performed gene expression profiling of the cerebral cortex and striatum of these animals and revealed insulin-like growth factor 2 (IGF2) as a major upregulated genes. Here, we studied the impact of IGF2 signaling in protein aggregation in the model of Huntington’s disease (HD) as a proof of concept.
cell culture studies showed that treatment IGF2 reduce the burden of mutant huntingtin aggregates intracellularly and the peptide Polyglutamine. These results were validated using induced pluripotent stem cells (IPSC) -derived medium spiny neurons of HD patients and cases of degenerative neurological diseases. Decreased levels of the mutant huntingtin protein is associated with a decrease in intracellular half-life. Decreased levels of the abnormal protein aggregation induced by IGF2 independent of autophagy activity and proteasome pathway, two major route clearance for mutant huntingtin.
Instead, IGF2 signaling increases the secretion of soluble mutant huntingtin species via exosomes and microvesicles involve changes in actin dynamics. Administration of IGF2 in HD mouse brain using gene therapy led to a significant reduction in the level of mutant huntingtin in three different animal models. In addition, analysis of postmortem brain tissue and human blood samples from HD patients showed decreased levels of IGF2. This study identifies factors that are relevant IGF2 as deregulation in HD, operates as a disease modifier that buffer accumulation of abnormal protein species.
Insulin–likegrowthfactor2 (IGF2) protects against Huntington’s disease through the extracellular disposal of protein aggregates
Effect of prenatal bisphenol A exposure on a body mass index of early childhood through the influence of epigenetics on insulin – like growth factor < em> 2 receptor (IGF two R) gene Objective: epigenetic mechanisms have been proposed to play a role in the link between exposure to the womb to bisphenol A (BPA) and childhood obesity; However, there is little evidence of this mechanism in humans.
We obtained data on obesity-associated CpG sites of epigenome-wide association study beforehand, and then examined whether methylation at CpG sites affected by prenatal exposure to BPA. We then evaluated the relationship between CpG methylation status and body mass index (BMI) in a prospective cohort of children at ages 2, 4, 6 and 8 years old.
Methods: The methylation profile of 59 children analyzed longitudinally at the age of 2 and 6 years using human Infinium Methylation BeadChip. A total of 594 CpG sites known to BMI or obesity-related sites were tested for association with prenatal BPA levels, are categorized into low and high exposure group based on the 80 percentile of maternal BPA levels (2.68 mg / g creatinine), followed by an analysis of the relationship between DNA methylation and BMI from ages 2-8.
Results: There was a significant increase in the level of methylation cg19196862 (IGF2R) at high BPA group at the age of 2 years (p = 0.00030, false discovery rate corrected p <0.10) but not at age 6. By one standard deviation increase in methylation The cg19196862 (IGF2R) at the age of 2 years, a linear mixed model analysis revealed that BMI for age 2-8 years significantly increased 0.49 (95% confidence interval; 0.08, 0.90) in girls, but not in boys.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: This gene encodes a member of the IGF-II mRNA-binding protein (IMP) family. The protein encoded by this gene contains four KH domains and two RRM domains. It functions by binding to the 5' UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulating IGF2 translation. Alternative promoter usage and alternate splicing result in multiple variants encoding different isoforms.
Description: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts.
Description: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts.
Description: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts.
Description: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IGF2BP2 (C-term). This antibody is tested and proven to work in the following applications:
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IGF2BP2 (C-term). This antibody is tested and proven to work in the following applications:
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with PE.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), PE
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with PE.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Human), APC
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with APC.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Human), Cy3
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with Cy3.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Human), FITC
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with FITC.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Human), HRP
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with HRP.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), APC
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with APC.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), Cy3
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with Cy3.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), FITC
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with FITC.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), HRP
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with HRP.
Polyclonal Antibody to Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2)
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with Biotin.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), Biotinylated
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with Biotin.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Human), APC-Cy7
Description: A Rabbit polyclonal antibody against Human Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with APC-Cy7.
Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) Polyclonal Antibody (Mouse), APC-Cy7
Description: A Rabbit polyclonal antibody against Mouse Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2). This antibody is labeled with APC-Cy7.
PE-Linked Polyclonal Antibody to Insulin Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2)
The indirect effect of prenatal BPA exposure during early childhood through methylation cg19196862 BMI (IGF2R) at the age of 2 years of marginal significance.
