Connecting myelin membrane turnover with antigen presenting cells and autoimmunity (A10)

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The project primarily aims to identify a connection between lipid toxicity and the pathogenesis of demyelinating diseases. A10 proposes that lipid overloading in microglia can induce a maladaptive immune response. In the current funding period A10 found that cholesterol crystals are formed in microglia/macrophages after inducing a demyelinating event. Such crystals are generated in lyosomes and may trigger lysosomal rupture, activate the inflammasome complex and induce pyroptosis. This project will test whether cholesterol overloading and crystal formation impairs tissue repair in demyelinating lesions. Novel experimental strategies of how to promote lipid efflux from demyelinating lesions in order to promote remyelination and protect neurons from degeneration will be tested.