Neuroinflammation and neuron-glia signalling through extracellular vesicles excreted during neuronal cell death in neurodegeneration.

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We hypothesise that the karyoptotic microvesicles up-taken by microglia, or one of their components, act as Damage Associated Molecular Pattern (DAMP) and may trigger metabolic changes in the microglia to respond to the neuronal cell death in the surroundings. It is however unclear whether this will be a pro-or anti-inflammatory response as it is equally possible that the entrapment in microvesicles is designed to quench the pro-inflammatory response elicited by nuclear DAMPs and degrade the signal. Both hypotheses will be tested in this project.This project will useneuronal cells from differentiated neuroblastoma expressing the C9ORF72 polyPR peptides and, in some contexts, derived from C9ORF72 patient's iPSC, and the partnership between labs will enable the student to gain both molecular and cellular neuroscience skillsets in order to address our aims.