Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease

Abstract

Parkinson's disease (PD) is a complex multifactorial disease characterized by the progressive loss of midbrain dopamine neurons. Sustained microglia-mediated neuroinflammation has been recognized as a major pathophysiological contributor to chronic degenerative processes in PD; however, the key molecular signaling mechanisms underlying microglial activation are not entirely clear. Herein, we identified a novel role for the non-receptor tyrosine kinase Fyn in regulating neuroinflammatory responses in microglia. Our data clearly suggest that the Fyn-PKCδ signaling axis acts as a major upstream signaling mediator of the sustained neuroinflammatory processes in cell culture and animal models of PD. Our finding has important clinical significance to PD because it identifies Fyn as a potential translational target for intervention of progressive neurodegenerative processes in PD.