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Project

Deciphering the contribution of progranulin deficient human microglia in the initiation and modification of frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most common form of dementia. It presents a heterogenous range of neuropathological hallmarks, including aberrant accumulation of TAU, FUS or TDP-43. FTD is also accompanied by inflammatory changes in the brain. Recent data place microglia, the immune cells of the brain, under the spotlight as central player in determining the susceptibility for developing FTD. In this proposal, we aim to define what is the role of one of the most relevant genetic causes of FTD, progranulin deficiency, in microglia using a combination of in vitro and in vivo approaches. We plan to generate independent series of genetically modified stem cells to partially or completely delete progranulin. Then, we will differentiate these cells into microglia to 1) study their basal alterations in in vitro systems, and 2) xenotransplant them in the mouse brain following our MIGRATE protocol. Using these cutting-edge in vivo systems, we expect to determine whether progranulin deficient microglia is sufficient to induce or can significantly modify FTD-like pathology. This project has major implications for our understanding of the cellular and molecular basis of FTD and will open new avenues for tailored treatments to tackle FTD progression.
Date:1 Oct 2022 →  Today
Keywords:MICROGLIA, FRONTOTEMPORAL DEMENTIA, NEUROINFLAMMATION, STEM CELLS
Disciplines:Neurological and neuromuscular diseases