Vasiliki Panagiotakopoulou, Dina Ivanyuk, Silvia De Cicco, Wadood Haq, Aleksandra Arsić, Cong Yu, Daria Messelodi, Marvin Oldrati, David C Schöndorf, Maria-Jose Perez, Ruggiero Pio Cassatella, Meike Jakobi, Nicole Schneiderhan-Marra, Thomas Gasser, Ivana Nikić-Spiegel, Michela Deleidi
Parkinson's disease-associated kinase LRRK2 has been linked to IFN type II (IFN-γ) response in infections and to dopaminergic neuronal loss. However, whether and how LRRK2 synergizes with IFN-γ remains unclear. In this study, we employed dopaminergic neurons and microglia differentiated from patient-derived induced pluripotent stem cells carrying LRRK2 G2019S, the most common Parkinson's disease-associated mutation. We show that IFN-γ enhances the LRRK2 G2019S-dependent negative regulation of AKT phosphorylation and NFAT activation, thereby increasing neuronal vulnerability to immune challenge...
October 14, 2020: Nature Communications