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Project

Xenotransplantation of iPSC derived microglia to decipher the impact of Progranulin in neuroinflammation and neurodegeneration.

Frontotemporal dementia (FTD) is a chronic neurodegenerative disease and is the second most common form of dementia worldwide. FTD is characterized by the build up of abnormal proteins inside nerve cells including TAU, FUS or TDP-43. FTD is accompanied by changes in the immune cells of the brain, the microglia. This inflammation in the brain is referred to as neuroinflammation, which may be a simple consequence of damage to nerve cells or may contribute to disease progression. FTD genetics has recently linked neuroinflammation and susceptibility to develop FTD, suggesting that inflammation might be a driver of the disease opposed to just a consequence. The current proposal is aimed at determining the role of one of the most important genetic causes of FTD, progranulin deficiency, by using novel models where human derived cells are injected into FTD mice, in order to expose those cells to the environment they would find in the pathological brain. By doing this with microglial cells, we will be able to dissect the contribution of progranulin in neuroinflammation and human microglia biology in FTD. These findings will have major implications for our understanding of the progression of human disease and would allow tailored treatments to slow down or arrest FTD progression. This approach addresses a critical component of the pathology of FTD and may yield novel drug targets with the potential to change the disease trajectory and patients' quality of life.
Date:1 Jan 2022 →  Today
Keywords:MICROGLIA, NEUROINFLAMMATION, STEM CELLS, FRONTOTEMPORAL DEMENTIA
Disciplines:Bioinformatics of disease, Innate immunity, Neurological and neuromuscular diseases, Stem cell biology