De rol van LRRK2 in neurodegeneratie en ontsteking in de ziekte van Parkinson

Parkinson's disease (PD) is the most common neurodegenerative motor disorder. No therapy can cure, stop or slow down the progression of the disease, as only symptomatic treatment strategies are available. Identifying pathogenic mechanisms underlying neurodegeneration will therefore be essential to develop a disease-modifying drug. PD is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of aggregates of misfolded α-synuclein (αSYN). Although the exact cause of neurodegeneration in PD remains unclear, there is currently no doubt that α-synuclein (αSYN) aggregation is a key pathogenic factor. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of familial PD, leading to a pathology and symptoms that are indistinguishable from sporadic PD patients. Mounting evidence supports the idea that peripheral immune cells are involved in neuroinflammation, which was for a long time considered as a consequence of neurodegeneration, but is now believed to play an active role in the disease pathogenesis. In this PhD project we aim to further unravel the role of the peripheral immune system in LRRK2- and αSYN-based rodent models of PD.