Hemo-Park

The immune system allows us to respond to external/internal insults. Moreover, through their ability to reach all tissues, immune cells are also involved in metabolic, neurodegenerative and autoimmune diseases, making them potential therapeutic targets. Parkinson’s disease (PD) is characterized by the degeneration of midbrain dopaminergic neurons, which causes motor symptoms and severe neurological disorders. PD is a multifactorial syndrome that is still not well understood to this day, associated with various cellular defects and neuroinflammatory processes, characterized by the increased abundance of activated microglia, the resident macrophages of the brain, and also the infiltration of peripheral immune cells. In this proposal, and based on our recent preliminary results, we aim to shed light on the role of neuroinflammation induced by brain-invading immune cells and activated glia in the progression of neurodegeneration using transgenic and drug-induced models of PD in Drosophila. The use of these two models will enable us to compare genetic and environmental conditions known to be involved in PD pathogenesis and provide better chance to discover innovative therapeutic targets. The objectives of this project, for which all the required tools and complementary expertise are available in the partners' teams, will be: - Aim 1: to identify the immune cell subpopulations that control the inflammatory process in the fly brain under neurodegenerative conditions, - Aim 2: to determine the specific role of these cells on brain inflammation and the progression of neurodegeneration, - Aim 3: to identify through transcriptomic analysis immune cell-dependent pathways that potentially modulate neurodegeneration. This program should provide a better understanding of the innate immune response of the brain and its physiopathological role, and help to prevent or cure human autoimmune or neurodegenerative diseases, which represent a heavy burden on our societies.