Abstract: Objective To investigate the interaction between ?-synuclein and Nurr1 and its influence on the production of TNF-?. Methods The association between ?-synuclein and Nurr1 was observed with Co-IP. The co-localization and the nuclear translocation level of Nurr1 was observed by immunocytochemistry. The BV2 cells were transfected with plasmid encoding pCMV-Myc-vector, pCMV-Myc-?-synuclein with/without Nurr1-pAAV for 24 hours, Media were collected and used Elisa to quantify the level of TNF-?. Result Immunocytochemistry images have shown that ?-synuclein was co-locolization with Nurrl, meanwhile, Co-IP results further showed that ?-synuclein may interacted with Nurr1. Nurr1 nuclear translocation level decreased and TNF-? production increased significantly in ?-synucein overexpression BV2 cells. However, Nurr1 could attenuate the increase of TNF-? induced by ?-synucein in double-transfected BV2 cells. Conclusion ?-Syn associated with Nurr1 and this association contributed to Nurr1 inactivation and its downstream gene TNF-?. The results may suggest that one of mechanisms of inflammation with glia activation induced by ?-synuclein, which might provide critical insights into the pathogenesis of PD and other neurodegenerative diseases.

Key words: α-synuclein , Nurr1, TNF-α, BV2 cells