{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:59:04Z","timestamp":1787021944470,"version":"build-2736575974"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T00:00:00Z","timestamp":1427414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0121072","type":"journal-article","created":{"date-parts":[[2015,3,28]],"date-time":"2015-03-28T22:30:19Z","timestamp":1427581819000},"page":"e0121072","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":61,"title":["A Nurr1 Agonist Causes Neuroprotection in a Parkinson\u2019s Disease Lesion Model Primed with the Toll-Like Receptor 3 dsRNA Inflammatory Stimulant Poly(I:C)"],"prefix":"10.1371","volume":"10","author":[{"given":"Gaynor A.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rooney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Barneoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse R.","family":"McLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Beagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresia","family":"Osborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Coimbra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope J.","family":"Hallett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Isacson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,3,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1423-0127-21-27","article-title":"The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed","volume":"21","author":"KN Alavian","year":"2014","journal-title":"J Biomed Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.pneurobio.2005.09.001","article-title":"The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease","volume":"77","author":"J Jankovic","year":"2005","journal-title":"Prog Neurobiol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-386986-9.00001-6","article-title":"The function and mechanisms of Nurr1 action in midbrain dopaminergic neurons, from development and maintenance to survival","volume":"102","author":"Y Luo","year":"2012","journal-title":"Int Rev Neurobiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/j.1460-9568.2004.03204.x","article-title":"Temporally induced Nurr1 can induce a non-neuronal dopaminergic cell type in embryonic stem cell differentiation","volume":"19","author":"KC Sonntag","year":"2004","journal-title":"Eur J Neurosci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0306-4522(99)00124-4","article-title":"Differential expression of tyrosine hydroxylase in catecholaminergic neurons of neonatal wild-type and Nurr1-deficient mice","volume":"93","author":"JS Baffi","year":"1999","journal-title":"Neuroscience"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/mds.20246","article-title":"Nurr1 mutational screen in Parkinson's disease","volume":"19","author":"EK Tan","year":"2004","journal-title":"Mov Disord"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/mds.20820","article-title":"Translated mutation in the Nurr1 gene as a cause for Parkinson's disease","volume":"21","author":"DA Grimes","year":"2006","journal-title":"Mov Disord"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1212\/01.WNL.0000118285.18383.90","article-title":"Extended mutation analysis and association studies of Nurr1 (NR4A2) in Parkinson disease","volume":"62","author":"R Hering","year":"2004","journal-title":"Neurology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0304-3940(03)00539-1","article-title":"Genetic analysis of Nurr1 haplotypes in Parkinson's disease","volume":"347","author":"EK Tan","year":"2003","journal-title":"Neurosci Lett"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/cne.10261","article-title":"Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra","volume":"450","author":"Y Chu","year":"2002","journal-title":"J Comp Neurol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00401-006-0181-6","article-title":"Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra","volume":"113","author":"LB Moran","year":"2007","journal-title":"Acta Neuropathol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/cne.20828","article-title":"Nurr1 in Parkinson's disease and related disorders","volume":"494","author":"Y Chu","year":"2006","journal-title":"J Comp Neurol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1001 e1007","DOI":"10.1016\/j.neurobiolaging.2011.03.022","article-title":"Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson's disease","volume":"33","author":"L Zhang","year":"2012","journal-title":"Neurobiol Aging"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1073\/pnas.1221077110","article-title":"Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons","volume":"110","author":"B Kadkhodaei","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1126\/science.276.5310.248","article-title":"Dopamine neuron agenesis in Nurr1-deficient mice","volume":"276","author":"RH Zetterstrom","year":"1997","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"163ra156","DOI":"10.1126\/scitranslmed.3004676","article-title":"alpha-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons","volume":"4","author":"M Decressac","year":"2012","journal-title":"Sci Transl Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1471-4159.2007.04494.x","article-title":"Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro","volume":"102","author":"F Volpicelli","year":"2007","journal-title":"J Neurochem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cell.2009.01.038","article-title":"A Nurr1\/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death","volume":"137","author":"K Saijo","year":"2009","journal-title":"Cell"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"121ps123","DOI":"10.1126\/scitranslmed.3003492","article-title":"Viral and inflammatory triggers of neurodegenerative diseases","volume":"4","author":"M Deleidi","year":"2012","journal-title":"Sci Transl Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"16091","DOI":"10.1523\/JNEUROSCI.2400-10.2010","article-title":"The Toll-like receptor-3 agonist polyinosinic:polycytidylic acid triggers nigrostriatal dopaminergic degeneration","volume":"30","author":"M Deleidi","year":"2010","journal-title":"J Neurosci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-2094-5-8","article-title":"Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease","volume":"5","author":"JB Koprich","year":"2008","journal-title":"J Neuroinflammation"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrneurol.2013.209","article-title":"NURR1 in Parkinson disease\u2014from pathogenesis to therapeutic potential","volume":"9","author":"M Decressac","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1242\/dev.095802","article-title":"Foxa2 acts as a co-activator potentiating expression of the Nurr1-induced DA phenotype via epigenetic regulation","volume":"141","author":"SH Yi","year":"2014","journal-title":"Development"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/1742-2094-8-166","article-title":"The acute inflammatory response to intranigral alpha-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation","volume":"8","author":"Y Couch","year":"2011","journal-title":"J Neuroinflammation"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"10825","DOI":"10.1523\/JNEUROSCI.3001-08.2008","article-title":"Parkin deficiency increases vulnerability to inflammation-related nigral degeneration","volume":"28","author":"TC Frank-Cannon","year":"2008","journal-title":"J Neurosci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1742-2094-10-50","article-title":"Analysis of inflammation-related nigral degeneration and locomotor function in DJ-1(-\/-) mice","volume":"10","author":"TA Nguyen","year":"2013","journal-title":"J Neuroinflammation"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1523\/JNEUROSCI.23-04-01228.2003","article-title":"Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease","volume":"23","author":"HM Gao","year":"2003","journal-title":"J Neurosci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.neurobiolaging.2007.11.020","article-title":"Inflammatory priming of the substantia nigra influences the impact of later paraquat exposure: Neuroimmune sensitization of neurodegeneration","volume":"30","author":"EN Mangano","year":"2009","journal-title":"Neurobiol Aging"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/j.1471-4159.2010.06841.x","article-title":"Nurr1 regulates RET expression in dopamine neurons of adult rat midbrain","volume":"114","author":"D Galleguillos","year":"2010","journal-title":"J Neurochem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1006\/mcne.2001.1057","article-title":"Orphan nuclear receptor Nurr1 is essential for Ret expression in midbrain dopamine neurons and in the brain stem","volume":"18","author":"AA Wallen","year":"2001","journal-title":"Mol Cell Neurosci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.brainresbull.2010.09.009","article-title":"Expressions and possible roles of GDNF receptors in the developing dopaminergic neurons","volume":"83","author":"JP Cao","year":"2010","journal-title":"Brain Res Bull"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/pr.2013.126","article-title":"Maternal inflammation promotes fetal microglial activation and increased cholinergic expression in the fetal basal forebrain: role of interleukin-6","volume":"74","author":"L Pratt","year":"2013","journal-title":"Pediatr Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.bbi.2010.04.004","article-title":"Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNalpha\/beta and IL-1beta responses in the diseased brain and exacerbates chronic neurodegeneration","volume":"24","author":"R Field","year":"2010","journal-title":"Brain Behav Immun"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/jnr.21958","article-title":"Peripheral challenge with double-stranded RNA elicits global up-regulation of cytokine gene expression in the brain","volume":"87","author":"GW Konat","year":"2009","journal-title":"J Neurosci Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.bbi.2006.12.005","article-title":"Influence of poly I:C on sickness behaviors, plasma cytokines, corticosterone and central monoamine activity: moderation by social stressors","volume":"21","author":"R Gandhi","year":"2007","journal-title":"Brain Behav Immun"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S1474-4422(09)70062-6","article-title":"Neuroinflammation in Parkinson's disease: a target for neuroprotection?","volume":"8","author":"EC Hirsch","year":"2009","journal-title":"Lancet Neurol"},{"key":"ref37","first-page":"952375","article-title":"Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson's disease","volume":"2013","author":"SV More","year":"2013","journal-title":"Mediators Inflamm"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s00401-003-0766-2","article-title":"Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains","volume":"106","author":"K Imamura","year":"2003","journal-title":"Acta Neuropathol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.neulet.2007.09.032","article-title":"Expression of FasL and its interaction with Fas are mediated by c-Jun N-terminal kinase (JNK) pathway in 6-OHDA-induced rat model of Parkinson disease","volume":"428","author":"J Pan","year":"2007","journal-title":"Neurosci Lett"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1523\/JNEUROSCI.4564-03.2004","article-title":"Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease","volume":"24","author":"S Hayley","year":"2004","journal-title":"J Neurosci"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fneur.2013.00018","article-title":"The role of markers of inflammation in traumatic brain injury","volume":"4","author":"T Woodcock","year":"2013","journal-title":"Front Neurol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000329568","article-title":"Role of interleukin 6 and alpha-globulins in differentiating Alzheimer and vascular dementias","volume":"9","author":"AA Helmy","year":"2012","journal-title":"Neurodegener Dis"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1097\/WNR.0b013e32832e34ee","article-title":"Distinct neuroinflammatory profile in post-mortem human Huntington's disease","volume":"20","author":"A Silvestroni","year":"2009","journal-title":"Neuroreport"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1523\/JNEUROSCI.5427-08.2009","article-title":"Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy","volume":"29","author":"CY Chung","year":"2009","journal-title":"J Neurosci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuroscience.2012.02.001","article-title":"Parkinson's disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity","volume":"208","author":"F Gillardon","year":"2012","journal-title":"Neuroscience"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"9289","DOI":"10.1073\/pnas.1403215111","article-title":"Abrogation of alpha-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats","volume":"111","author":"JP Daher","year":"2014","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0121072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T22:29:27Z","timestamp":1717799367000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0121072"}},"subtitle":[],"editor":[{"given":"Mal\u00fa G.","family":"Tansey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,27]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0121072","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,27]]}}}