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Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a DNA-RNA binding protein encoded by the Tardbp gene, as a strong regulator of microglial phagocytosis. Mice lacking TDP-43 in microglia exhibit reduced amyloid load in a model of Alzheimer's disease (AD) but at the same time display drastic synapse loss, even in the absence of amyloid. Clinical examination from TDP-43 pathology cases reveal a considerably reduced prevalence of AD and decreased amyloid pathology compared to age-matched healthy controls, confirming our experimental results. Overall, our data suggest that dysfunctional microglia might play a causative role in the pathogenesis of neurodegenerative disorders, critically modulating the early stages of cognitive decline.
Pubmed ID: 28669544 RIS Download
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Commercial antibody supplier and developer for biomedical research. These products are compatible with use in flow cytometry and mass cytometry, immunoprecipitation and chip, western blotting, immunofluorescence microscopy, and quantitative multiplexing.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsProteintech Europe Ltd is an ISO 9001:2008 certified company
View all literature mentionsStudy testing whether strict glucose control lowers the risk of heart disease and stroke in adults with type 2 diabetes. In addition the study is exploring: 1) Whether in the context of good glycemic control the use of different lowering lipid drugs will further improve these outcomes and 2) If strict control of blood pressure will also have additional beneficial effects on reducing cardiovascular disease. The design was a randomized, multicenter, double 2 X 2 factorial trial in 10,251 patients with type 2 diabetes mellitus. It was designed to test the effects on major CVD events of intensive glycemia control, of fibrate treatment to increase HDL-cholesterol and lower triglycerides (in the context of good LDL-C and glycemia control), and of intensive blood pressure control (in the context of good glycemia control), each compared to an appropriate control. All 10,251 participants were in an overarching glycemia trial. In addition, one 2 X 2 trial addressed the lipid question in 5,518 of the participants and the other 2 X 2 trial addressed the blood pressure question in 4,733 of the participants. The glycemia trial was terminated early due to higher mortality in the intensive compared with the standard glycemia treatment strategies. The results were published in June 2008 (N Eng J Med 2008;358:2545-59). Study-delivered treatment for all ACCORD participants was stopped on June 30, 2009, and the participants were assisted as needed in transferring their care to a personal physician. The lipid and blood pressure results (as well as the microvascular outcomes and eye substudy results) were published in 2010. All participants are continuing to be followed in a non-treatment observational study.
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View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsCell line BV-2 is a Transformed cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name B6(SJL)-Tardbptm1.1Pcw/J from IMSR.
View all literature mentionsMus musculus with name B6(SJL)-Tardbptm1.1Pcw/J from IMSR.
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