Abstract
Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders. Alpha-synuclein (α-Syn) aggregation and propagation play a central role in PD pathology, yet the cellular mechanisms driving these processes remain unclear. Recent studies suggest that in 'body-first' PD, α-Syn pathology originates in peripheral tissues, particularly the enteric nervous system, before migrating to the brain via the vagus nerve. We hypothesize that muscularis macrophages, a subset of innate immune cells in the gut, modulate α-Syn pathology and its spreading to the brain. We will elucidate the signalling pathways and immune cells involved in α-Syn migration and immune responses along the gut-brain axis. We will apply cutting-edge in vivo labelling techniques to (i) map the immune interactions of muscularis macrophages and (ii) identify the secreted signals driving immune cell recruitment to the brain. Our findings will not only advance our understanding of the peripheral immune mechanisms governing PD but also provide novel insights for the development of therapeutic strategies targeting early disease intervention.
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