Team Lashuel

Parkinson’s disease (PD) is characterized by α-synuclein (α-syn) aggregation, Lewy body (LB) formation, and neurodegeneration, with lysosomal dysfunction playing a key role in pathogenesis. Using a novel triculture model of dopaminergic neurons, astrocytes, and microglia, we will investigate how neuron-glia interactions influence α-syn clearance and pathology. Following this integrative approach, we will assess the effects of PD-associated lysosomal gene mutations, including LRRK2, TMEM175, and ATP13A2, on lysosomal activity, α-syn degradation, aggregate formation, and neurodegeneration. Finally, we will examine the relationship between lysosomal dysfunction, α-syn clearance, and neuroinflammation and explore therapeutic strategies to enhance α-syn clearance, aiming to identify neuroprotective targets.