INVESTIGATING NEUROINFLAMMATION IN SPORADIC AND LRRK2-ASSOCIATED PARKINSON'S DISEASE

Inflammatory responses are evolutionarily conserved reactions to pathogens, injury, or any form of a serious perturbation of a human organism. These mechanisms evolved together with us and, although capable of somewhat adapting, innate responses are gravely impacted by prolonged human lifespan. Better sanitary measures, health systems, food and medicine supply have prolonged human life expectancy to ~72 years. Aging is characterized by prolonged, chronic (often low-grade) inflammation. With tissue and cellular defense mechanisms becoming dysfunctional over time, this inflammation becomes detrimental and destructive to the human body. Aging is a major risk factor for Parkinson’s disease (PD), a movement disorder characterized by the loss of dopaminergic neurons. Even though the disease is predominantly idiopathic, genetic cases are contributing to a better understanding of the underlying cellular and neuropathological mechanisms. In comparison to neuronal demise, the contribution of microglia (the immune cells of the brain) to PD is relatively understudied. Initially studied in PD patient-derived post-mortem tissue, novel in vitro technologies, such as induced pluripotent stem cells (iPSCs), are permitting the generation of specific cell types of interest in order to study disease mechanisms. We derived microglia cells from iPSCs of patients and healthy or isogenic controls to explore (shared) pathological immune responses in LRRK2-PD and idiopathic PD. Our findings suggest a significant involvement of microglia cells in the pathogenesis of PD and highlight potential therapeutic targets in alleviating overactive immune responses