Reducing Igf-1r levels leads to paradoxical and sexually dimorphic effects in HD mice
| العنوان: | Reducing Igf-1r levels leads to paradoxical and sexually dimorphic effects in HD mice |
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| المؤلفون: | Joel May, Michelle Stewart, Steve D.M. Brown, Gillian P. Bates, Sarah K. Carter, Abraham Acevedo-Arozena, David C. Rubinsztein, Maurizio Renna, Georgina F. Osborne, Silvia Corrochano |
| المساهمون: | Corrochano, Silvia, Renna, Maurizio, Osborne, Georgina, Carter, Sarah, Stewart, Michelle, May, Joel, Bates, Gillian P., Brown, Steve D. M., Rubinsztein, David C., Acevedo-Arozena, Abraham |
| المصدر: | PLoS ONE, Vol 9, Iss 8, p e105595 (2014) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Huntingtin, Physiology, medicine.medical_treatment, Peptide Hormones, Sex Factor, Biochemistry, Receptor, IGF Type 1, Mice, Endocrinology, Cell Signaling, Insulin Signaling Cascade, Molecular Cell Biology, Neurobiology of Disease and Regeneration, Medicine and Health Sciences, Insulin, Receptor, Multidisciplinary, Neurodegenerative Diseases, Animal Models, Signaling Cascades, Huntington Disease, Phenotype, Neurology, Medicine, Female, Anatomy, Genetic Dominance, Research Article, Signal Transduction, medicine.medical_specialty, Heterozygote, Science, Endocrine System, Mouse Models, Biology, Research and Analysis Methods, Sex Factors, Model Organisms, Growth factor receptor, Insulin-like Growth Factors, Internal medicine, Autosomal Dominant Traits, medicine, Genetics, Animals, PI3K/AKT/mTOR pathway, Biochemistry, Genetics and Molecular Biology (all), Endocrine Physiology, Animal, Growth factor, Autophagy, Autosomal Dominant Diseases, Biology and Life Sciences, Human Genetics, Cell Biology, Hormones, Mice, Inbred C57BL, Agricultural and Biological Sciences (all), Ageing, Immunology, Genetics of Disease, Molecular Neuroscience, Gene Deletion, Neuroscience |
| الوصف: | Many of the neurodegenerative diseases that afflict people in later life are associated with the formation of protein aggregates. These so-called “proteinopathies” include Alzheimer’s disease (AD) and Huntington’s disease (HD). The insulin/insulin-like growth factor signalling (IIS) pathway has been proposed to modulate such diseases in model organisms, as well as the general ageing process. In this pathway, insulin-like growth factor binds to insulin-like growth factor receptors, such as the insulin-like growth factor 1 receptor (IGF-1R). Heterozygous deletion of Igf-1r has been shown to lead to increased lifespan in mice. Reducing the activity of this pathway had benefits in a HD C. elegans model, and some of these may be attributed to the expected inhibition of mTOR activity resulting in an increase in autophagy, which would enhance mutant huntingtin clearance. Thus, we tested if heterozygous deletion of Igf-1r would lead to benefits in HD related phenotypes in the mouse. Surprisingly, reducing Igf-1r levels led to some beneficial effects in HD females, but also led to some detrimental effects in HD males. Interestingly, Igf-1r deficiency had no discernible effects on downstream mTOR signalling in HD mice. These results do not support a broad beneficial effect of diminishing the IIS pathway in HD pathology in a mammalian system. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d5b0dc21ed8201847bbebb3da2425c8Test https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25140802/pdf/?tool=EBITest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0d5b0dc21ed8201847bbebb3da2425c8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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