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Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia\u2010mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied by microglia activation in response to lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) <jats:italic>in\u00a0vitro<\/jats:italic> and in experimental 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> mouse model. Nur77 over\u2010expression or application of Nur77 agonist cytosporone B suppressed the expression of proinflammatory genes, such as inducible nitric oxide NOS, cyclooxygenase\u20102, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2, and tumor necrosis factor\u2010\u03b1 in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia. Moreover, activation of Nur77 suppressed the <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation which was partly dependent on p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activity, since inhibition of p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> by <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>203580 abolished the <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010activated <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB in microglia. On the other hand, inhibition of p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> attenuated <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced Nur77 reduction. Furthermore, in a microglia\u2010conditioned cultured media system, Nur77 ameliorated the cytotoxicity to <jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>9D dopaminergic cells. Lastly, cytosporone B attenuated microglia activation and loss of dopaminergic neuron in the substantia nigra pars compacta (<jats:styled-content style=\"fixed-case\">SN<\/jats:styled-content>pc) of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> mouse model. Taken together, these findings revealed the first evidence that Nur77 was an important modulator in microglia function that associated with microglia\u2010mediated dopaminergic neurotoxicity, and thus modulation of Nur77 may represent a potential novel target for treatment for neurodegenerative disease.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13907-fig-0011-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13907","type":"journal-article","created":{"date-parts":[[2016,11,27]],"date-time":"2016-11-27T09:02:48Z","timestamp":1480237368000},"page":"589-604","source":"Crossref","is-referenced-by-count":44,"title":["Activation of Nur77 in microglia attenuates proinflammatory mediators production and protects dopaminergic neurons from inflammation\u2010induced cell death"],"prefix":"10.1111","volume":"140","author":[{"given":"Tian\u2010Ya","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Translational Research and Therapy for Neuro\u2010Psycho\u2010Diseases and College of Pharmaceutical Sciences Soochow University Suzhou Jiangsu China"},{"name":"College of Pharmaceutical Sciences and the Collaborative Innovation Center for Brain Science Soochow University Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Translational Research and Therapy for Neuro\u2010Psycho\u2010Diseases and College of Pharmaceutical Sciences Soochow University Suzhou Jiangsu China"},{"name":"College of Pharmaceutical Sciences and the Collaborative Innovation Center for Brain Science Soochow University Suzhou 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