Biology

Dr. Nikhil Panicker
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Abstract:

Sustained neuroinflammation and progressive alpha-synuclein (Syn) aggregation are hallmarks of Parkinson’s disease (PD). The Nod like Receptor Protein (NLRP3) inflammasome is a multi-protein complex that constitutes a major arm of the innate immune system. Hyperactivation of the NLRP3 inflammasome within resident brain microglia has been demonstrated in neurodegenerative disorders. This complex has a two-step activation process (priming and activation) in order for it to attain functionality. The signaling mechanisms that govern NLRP3 inflammasome assembly within microglia are almost completely uncharacterized. We demonstrate that misfolded Syn can prime and activate the NLRP3 inflammasome in microglia, leading to increased neuroinflammation in PD. We also show that the non-receptor tyrosine kinase Fyn contributes to both these processes, feeding into PD-associated inflammasome assembly. Ongoing studies investigate how the inflammasome may also be activated in neurons in PD.