{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:43Z","timestamp":1792785823457,"version":"4.5.0"},"reference-count":122,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T00:00:00Z","timestamp":1521590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Cancer Center Support","award":["P30 CA021765"],"award-info":[{"award-number":["P30 CA021765"]}]},{"name":"The American-Lebanese Syrian Associated Charity"},{"DOI":"10.13039\/100008513","name":"Thomas Jefferson University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008513","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene result in late-onset Parkinson\u2019s disease. The incomplete penetrance of LRRK2 mutations in humans and LRRK2 murine models of Parkinson\u2019s disease suggests that the disease may result from a complex interplay of genetic predispositions and persistent exogenous insults. Since neuroinflammation is commonly associated with the pathogenesis of Parkinson\u2019s disease, we examine a potential role of mutant LRRK2 in regulation of the immune response and inflammatory signalling in vivo. Here, we show that mice overexpressing human pathogenic LRRK2 mutations, but not wild-type mice or mice overexpressing human wild-type LRRK2 exhibit long-term lipopolysaccharide-induced nigral neuronal loss. This neurodegeneration is accompanied by an exacerbated neuroinflammation in the brain. The increased immune response in the brain of mutant mice subsequently has an effect on neurons by inducing intraneuronal LRRK2 upregulation. However, the enhanced neuroinflammation is unlikely to be triggered by dysfunctional microglia or infiltrated T cells and\/or monocytes, but by peripheral circulating inflammatory molecules. Analysis of cytokine kinetics and inflammatory pathways in the peripheral immune cells demonstrates that LRRK2 mutation alters type II interferon immune response, suggesting that this increased neuroinflammatory response may arise outside the central nervous system. Overall, this study suggests that peripheral immune signalling plays an unexpected\u2014but important\u2014role in the regulation of neurodegeneration in LRRK2-associated Parkinson\u2019s disease, and provides new targets for interfering with the onset and progression of the disease.<\/jats:p>","DOI":"10.1093\/brain\/awy077","type":"journal-article","created":{"date-parts":[[2018,3,4]],"date-time":"2018-03-04T07:06:51Z","timestamp":1520147211000},"page":"1753-1769","source":"Crossref","is-referenced-by-count":140,"title":["Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo"],"prefix":"10.1093","volume":"141","author":[{"given":"Elena","family":"Kozina","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"},{"name":"Department of Neurosciences, Jefferson Hospital for Neuroscience, Thomas Jefferson University, 900 Walnut St, Philadelphia PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar","family":"Sadasivan","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Jiao","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"},{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Dou","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Tan","sequence":"first","affiliation":[{"name":"St. Jude Proteomics Facility, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Kodali","sequence":"first","affiliation":[{"name":"St. Jude Proteomics Facility, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Shaw","sequence":"first","affiliation":[{"name":"St. Jude Proteomics Facility, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"},{"name":"Department of Computational Biology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmin","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"},{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"},{"name":"St. Jude Proteomics Facility, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8459-5472","authenticated-orcid":false,"given":"Richard J","family":"Smeyne","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, 262 Danny Thomas Blvd, Memphis TN 38105, USA"},{"name":"Department of Neurosciences, Jefferson Hospital for Neuroscience, Thomas Jefferson University, 900 Walnut St, Philadelphia PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,3,21]]},"reference":[{"key":"2020042911360178800_awy077-B1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/35094583","article-title":"Cytokines and acute neurodegeneration","volume":"2","author":"Allan","year":"2001","journal-title":"Nat Rev Neurosci"},{"key":"2020042911360178800_awy077-B2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nri1664","article-title":"Interleukin-1 and neuronal injury","volume":"5","author":"Allan","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"2020042911360178800_awy077-B3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1159\/000097202","article-title":"Passage of cytokines across the blood-brain barrier","volume":"2","author":"Banks","year":"1995","journal-title":"Neuroimmunomodulation"},{"key":"2020042911360178800_awy077-B4","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbi.2009.09.001","article-title":"Minimal penetration of lipopolysaccharide across the murine blood-brain barrier","volume":"24","author":"Banks","year":"2010","journal-title":"Brain Behav Immun"},{"key":"2020042911360178800_awy077-B5","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.neuroscience.2009.04.031","article-title":"A comparison of model-based (2D) and design-based (3D) stereological methods for estimating cell number in the substantia nigra pars compacta (SNpc) of the C57BL\/6J mouse","volume":"161","author":"Baquet","year":"2009","journal-title":"Neuroscience"},{"key":"2020042911360178800_awy077-B6","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1177\/0891988710383572","article-title":"The genetics of Parkinson disease","volume":"23","author":"Bekris","year":"2010","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"2020042911360178800_awy077-B7","doi-asserted-by":"crossref","first-page":"E1738","DOI":"10.1073\/pnas.1525528113","article-title":"New tools for studying microglia in the mouse and human CNS","volume":"113","author":"Bennett","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020042911360178800_awy077-B8","doi-asserted-by":"crossref","first-page":"e70249","DOI":"10.1371\/journal.pone.0070249","article-title":"Non-motor and motor features in LRRK2 transgenic mice","volume":"8","author":"Bichler","year":"2013","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B9","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/ana.21019","article-title":"Localization of LRRK2 to membranous and vesicular structures in mammalian brain","volume":"60","author":"Biskup","year":"2006","journal-title":"Ann Neurol"},{"key":"2020042911360178800_awy077-B10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s40478-016-0396-2","article-title":"LRRK2 contributes to monocyte dysregulation in Parkinson's disease","volume":"4","author":"Bliederhaeuser","year":"2016","journal-title":"Acta Neuropathol Commun"},{"key":"2020042911360178800_awy077-B11","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1007\/s11064-007-9324-y","article-title":"LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson's disease","volume":"32","author":"Bonifati","year":"2007","journal-title":"Neurochem Res"},{"key":"2020042911360178800_awy077-B12","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/nprot.2007.207","article-title":"Isolation and culture of adult neurons and neurospheres","volume":"2","author":"Brewer","year":"2007","journal-title":"Nat Protoc"},{"key":"2020042911360178800_awy077-B13","first-page":"182","article-title":"Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease","volume":"119","author":"Brochard","year":"2009","journal-title":"J Clin Invest"},{"key":"2020042911360178800_awy077-B14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.neulet.2008.06.040","article-title":"Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism","volume":"441","author":"Brodacki","year":"2008","journal-title":"Neurosci Lett"},{"key":"2020042911360178800_awy077-B15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a unique TGF-beta-dependent molecular and functional signature in microglia","volume":"17","author":"Butovsky","year":"2014","journal-title":"Nat Neurosci"},{"key":"2020042911360178800_awy077-B16","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1038\/nprot.2006.327","article-title":"Isolation of murine microglial cells for RNA analysis or flow cytometry","volume":"1","author":"Cardona","year":"2006","journal-title":"Nat Protoc"},{"key":"2020042911360178800_awy077-B17","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1038\/ncomms4633","article-title":"MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration","volume":"5","author":"Cebrian","year":"2014","journal-title":"Nat Commun"},{"key":"2020042911360178800_awy077-B18","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/nn.2829","article-title":"Interferon-gamma induces progressive nigrostriatal degeneration and basal ganglia calcification","volume":"14","author":"Chakrabarty","year":"2011","journal-title":"Nat Neurosci"},{"key":"2020042911360178800_awy077-B19","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1523\/JNEUROSCI.4268-04.2005","article-title":"Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines","volume":"25","author":"Chakravarty","year":"2005","journal-title":"J Neurosci"},{"key":"2020042911360178800_awy077-B20","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.celrep.2013.06.018","article-title":"A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model","volume":"4","author":"Chiu","year":"2013","journal-title":"Cell Rep"},{"key":"2020042911360178800_awy077-B21","doi-asserted-by":"crossref","first-page":"9289","DOI":"10.1073\/pnas.1403215111","article-title":"Abrogation of \u03b1-synuclein\u2013mediated dopaminergic neurodegeneration in LRRK2-deficient rats","volume":"111","author":"Daher","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020042911360178800_awy077-B22","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1007\/s00018-013-1352-y","article-title":"The role of inflammation in sporadic and familial Parkinson's disease","volume":"70","author":"Deleidi","year":"2013","journal-title":"Cell Mol Life Sci"},{"key":"2020042911360178800_awy077-B23","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.parkreldis.2008.05.014","article-title":"Serum inflammatory biomarkers in Parkinson's disease","volume":"15","author":"Dufek","year":"2009","journal-title":"Parkinsonism Relat Disord"},{"key":"2020042911360178800_awy077-B24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/mds.26892","article-title":"LRRK2 levels and phosphorylation in Parkinson's disease brain and cases with restricted Lewy bodies","volume":"32","author":"Dzamko","year":"2017","journal-title":"Mov Disord"},{"key":"2020042911360178800_awy077-B25","doi-asserted-by":"crossref","first-page":"e39132","DOI":"10.1371\/journal.pone.0039132","article-title":"The IkappaB kinase family phosphorylates the Parkinson's disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling","volume":"7","author":"Dzamko","year":"2012","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B26","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/mds.26529","article-title":"Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers","volume":"31","author":"Dzamko","year":"2016","journal-title":"Mov Disord"},{"key":"2020042911360178800_awy077-B27","doi-asserted-by":"crossref","first-page":"e0004412","DOI":"10.1371\/journal.pntd.0004412","article-title":"A Missense LRRK2 variant is a risk factor for excessive inflammatory responses in leprosy","volume":"10","author":"Fava","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"2020042911360178800_awy077-B28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jneumeth.2005.06.026","article-title":"Rapid isolation of highly enriched and quiescent microglia from adult rat hippocampus: immunophenotypic and functional characteristics","volume":"151","author":"Frank","year":"2006","journal-title":"J Neurosci Methods"},{"key":"2020042911360178800_awy077-B29","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ng.717","article-title":"Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci","volume":"42","author":"Franke","year":"2010","journal-title":"Nat Genet"},{"key":"2020042911360178800_awy077-B30","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/ana.20484","article-title":"An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family","volume":"57","author":"Funayama","year":"2005","journal-title":"Ann Neurol"},{"key":"2020042911360178800_awy077-B31","first-page":"273","article-title":"Leucine-Rich Repeat kinase 2 G2385R variant is a risk factor for Parkinson disease in Asian population","volume":"18","author":"Funayama","year":"2006","journal-title":"Mol Neurosci"},{"key":"2020042911360178800_awy077-B32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1001\/archneur.63.3.377","article-title":"LRRK2 mutations in Spanish patients with Parkinson disease","volume":"63","author":"Gaig","year":"2006","journal-title":"Arch Neurol"},{"key":"2020042911360178800_awy077-B33","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.4049\/jimmunol.1000548","article-title":"LRRK2 is involved in the IFN-gamma response and host response to pathogens","volume":"185","author":"Gardet","year":"2010","journal-title":"J Immunol"},{"key":"2020042911360178800_awy077-B34","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":"Gillardon","year":"2012","journal-title":"Neuroscience"},{"key":"2020042911360178800_awy077-B35","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1212\/01.wnl.0000254483.19854.ef","article-title":"Evaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in Parkinson disease","volume":"68","author":"Goldwurm","year":"2007","journal-title":"Neurology"},{"key":"2020042911360178800_awy077-B36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10048-008-0162-0","article-title":"LRRK2 G2019S and R1441G mutations associated with Parkinson's disease are common in the Basque Country, but relative prevalence is determined by ethnicity","volume":"10","author":"Gorostidi","year":"2009","journal-title":"Neurogenetics"},{"key":"2020042911360178800_awy077-B37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.nbd.2006.04.001","article-title":"Kinase activity is required for the toxic effects of mutant LRRK2\/dardarin","volume":"23","author":"Greggio","year":"2006","journal-title":"Neurobiol Dis"},{"key":"2020042911360178800_awy077-B38","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jneumeth.2011.08.045","article-title":"FACS purification of immunolabeled cell types from adult rat brain","volume":"203","author":"Guez-Barber","year":"2012","journal-title":"J Neurosci Methods"},{"key":"2020042911360178800_awy077-B39","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00702-011-0653-2","article-title":"Parkinson's disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures","volume":"118","author":"Hakimi","year":"2011","journal-title":"J Neural Transm"},{"issue":"16 Pt 2","key":"2020042911360178800_awy077-B40","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1212\/01.wnl.0000304044.22253.03","article-title":"Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease","volume":"70","author":"Haugarvoll","year":"2008","journal-title":"Neurology"},{"key":"2020042911360178800_awy077-B41","doi-asserted-by":"crossref","first-page":"S205","DOI":"10.1016\/S1353-8020(09)70815-6","article-title":"Clinical features of LRRK2 parkinsonism","volume":"15","author":"Haugarvoll","year":"2009","journal-title":"Parkinsonism Relat Disord"},{"key":"2020042911360178800_awy077-B42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S1474-4422(08)70117-0","article-title":"Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study","volume":"7","author":"Healy","year":"2008","journal-title":"Lancet Neurol"},{"key":"2020042911360178800_awy077-B43","doi-asserted-by":"crossref","first-page":"e36581","DOI":"10.1371\/journal.pone.0036581","article-title":"High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in mouse brain","volume":"7","author":"Herzig","year":"2012","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B44","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1093\/hmg\/ddr348","article-title":"LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice","volume":"20","author":"Herzig","year":"2011","journal-title":"Hum Mol Genet"},{"key":"2020042911360178800_awy077-B45","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/j.1471-4159.2006.04246.x","article-title":"Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain","volume":"100","author":"Higashi","year":"2007","journal-title":"J Neurochem"},{"key":"2020042911360178800_awy077-B46","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1007\/s11064-009-9921-z","article-title":"Interleukin-6 serum levels in patients with Parkinson's disease","volume":"34","author":"Hofmann","year":"2009","journal-title":"Neurochem Res"},{"key":"2020042911360178800_awy077-B47","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s12031-014-0312-9","article-title":"The role of LRRK2 in the regulation of monocyte adhesion to endothelial cells","volume":"55","author":"Hongge","year":"2015","journal-title":"J Mol Neurosci"},{"key":"2020042911360178800_awy077-B48","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1042\/BJ20070209","article-title":"LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity","volume":"405","author":"Jaleel","year":"2007","journal-title":"Biochem J"},{"key":"2020042911360178800_awy077-B49","doi-asserted-by":"crossref","first-page":"14063","DOI":"10.1073\/pnas.0900096106","article-title":"Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration","volume":"106","author":"Jang","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020042911360178800_awy077-B50","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1002\/glia.20571","article-title":"Resident microglia die and infiltrated neutrophils and monocytes become major inflammatory cells in lipopolysaccharide-injected brain","volume":"55","author":"Ji","year":"2007","journal-title":"Glia"},{"issue":"Pt 12","key":"2020042911360178800_awy077-B51","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1093\/brain\/awh667","article-title":"Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data","volume":"128","author":"Khan","year":"2005","journal-title":"Brain"},{"key":"2020042911360178800_awy077-B52","doi-asserted-by":"crossref","first-page":"e34693","DOI":"10.1371\/journal.pone.0034693","article-title":"Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia","volume":"7","author":"Kim","year":"2012","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B53","doi-asserted-by":"crossref","first-page":"6455","DOI":"10.1111\/j.1742-4658.2009.07344.x","article-title":"LRRK2 in Parkinson's disease: genetic and clinical studies from patients","volume":"276","author":"Kumari","year":"2009","journal-title":"FEBS J"},{"key":"2020042911360178800_awy077-B54","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/jnc.12668","article-title":"Interferon-gamma induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages","volume":"129","author":"Kuss","year":"2014","journal-title":"J Neurochem"},{"key":"2020042911360178800_awy077-B55","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1042\/BJ20150985","article-title":"The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research","volume":"473","author":"Langston","year":"2016","journal-title":"Biochem J"},{"key":"2020042911360178800_awy077-B56","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1741-7015-6-32","article-title":"The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study","volume":"6","author":"Latourelle","year":"2008","journal-title":"BMC Med"},{"key":"2020042911360178800_awy077-B57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0306-4522(90)90229-W","article-title":"Heterogeneity in the distribution and morphology of microcroglia in the normal adult mouse brain","volume":"39","author":"Lawson","year":"1990","journal-title":"Neuroscience"},{"key":"2020042911360178800_awy077-B58","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/nm.2199","article-title":"Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease","volume":"16","author":"Lee","year":"2010","journal-title":"Nat Med"},{"key":"2020042911360178800_awy077-B59","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-62703-520-0_3","article-title":"Microglia isolation from adult mouse brain","volume":"1041","author":"Lee","year":"2013","journal-title":"Methods Mol Biol"},{"key":"2020042911360178800_awy077-B60","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1177\/1535370215579162","article-title":"LRRK2 mutations and neurotoxicant susceptibility","volume":"240","author":"Lee","year":"2015","journal-title":"Exp Biol Med"},{"key":"2020042911360178800_awy077-B61","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMc055540","article-title":"LRRK2 G2019S as a cause of Parkinson\u2019s disease in North African Arabs","volume":"354","author":"Lesage","year":"2006","journal-title":"N Engl J Med"},{"key":"2020042911360178800_awy077-B62","doi-asserted-by":"crossref","first-page":"pe2","DOI":"10.1126\/scisignal.2002680","article-title":"LRRK2 and human disease: a complicated question or a question of complexes?","volume":"5","author":"Lewis","year":"2012","journal-title":"Sci Signal"},{"key":"2020042911360178800_awy077-B63","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1523\/JNEUROSCI.5604-09.2010","article-title":"Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S","volume":"30","author":"Li","year":"2010","journal-title":"J Neurosci"},{"key":"2020042911360178800_awy077-B64","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nn.2349","article-title":"Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease","volume":"12","author":"Li","year":"2009","journal-title":"Nat Neurosci"},{"key":"2020042911360178800_awy077-B65","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/cr.2012.42","article-title":"The role of LRRK2 in inflammatory bowel disease","volume":"22","author":"Liu","year":"2012","journal-title":"Cell Res"},{"key":"2020042911360178800_awy077-B66","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.nbd.2014.07.013","article-title":"Genetic and pharmacological evidence that G2019S LRRK2 confers a hyperkinetic phenotype, resistant to motor decline associated with aging","volume":"71","author":"Longo","year":"2014","journal-title":"Neurobiol Dis"},{"key":"2020042911360178800_awy077-B67","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.parkreldis.2005.09.003","article-title":"The LRRK2 I2012T, G2019S, and I2020T mutations are rare in Taiwanese patients with sporadic Parkinson's disease","volume":"11","author":"Lu","year":"2005","journal-title":"Parkinsonism Relat Disord"},{"key":"2020042911360178800_awy077-B68","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1093\/hmg\/ddm151","article-title":"Mechanistic insight into the dominant mode of the Parkinson's disease-associated G2019S LRRK2 mutation","volume":"16","author":"Luzon-Toro","year":"2007","journal-title":"Hum Mol Genet"},{"key":"2020042911360178800_awy077-B69","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1750-1326-7-15","article-title":"The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities","volume":"7","author":"Maekawa","year":"2012","journal-title":"Mol Neurodegener"},{"key":"2020042911360178800_awy077-B70","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.nbd.2012.07.017","article-title":"LRRK2 expression is enriched in the striosomal compartment of mouse striatum","volume":"48","author":"Mandemakers","year":"2012","journal-title":"Neurobiol Dis"},{"key":"2020042911360178800_awy077-B71","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.neurobiolaging.2011.02.016","article-title":"Interferon- plays a role in paraquat-induced neurodegeneration involving oxidative and proinflammatory pathways","volume":"33","author":"Mangano","year":"2012","journal-title":"Neurobiol Aging"},{"key":"2020042911360178800_awy077-B72","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/BF00689592","article-title":"Expression of the histocompatibility glycoprotein HLA-DR in neurological disease","volume":"76","author":"McGeer","year":"1988","journal-title":"Acta Neuropathol"},{"key":"2020042911360178800_awy077-B73","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.nbd.2010.07.010","article-title":"Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice","volume":"40","author":"Melrose","year":"2010","journal-title":"Neurobiol Dis"},{"key":"2020042911360178800_awy077-B74","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.1093\/hmg\/ddv105","article-title":"Lack of exacerbation of neurodegeneration in a double transgenic mouse model of mutant LRRK2 and tau","volume":"24","author":"Mikhail","year":"2015","journal-title":"Hum Mol Genet"},{"key":"2020042911360178800_awy077-B75","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1038\/nn2015","article-title":"Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions","volume":"10","author":"Mildner","year":"2007","journal-title":"Nat Neurosci"},{"key":"2020042911360178800_awy077-B76","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1096\/fj.07-099499","article-title":"Interferon-gamma directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-gamma receptor and AMPA GluR1 receptor","volume":"22","author":"Mizuno","year":"2008","journal-title":"FASEB J"},{"key":"2020042911360178800_awy077-B77","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4049\/jimmunol.1100421","article-title":"The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood","volume":"188","author":"Mizutani","year":"2012","journal-title":"J Immunol"},{"key":"2020042911360178800_awy077-B78","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1093\/hmg\/ddv157","article-title":"The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins","volume":"24","author":"Moehle","year":"2015","journal-title":"Hum Mol Genet"},{"key":"2020042911360178800_awy077-B79","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1523\/JNEUROSCI.5601-11.2012","article-title":"LRRK2 inhibition attenuates microglial inflammatory responses","volume":"32","author":"Moehle","year":"2012","journal-title":"J Neurosci"},{"key":"2020042911360178800_awy077-B80","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jneumeth.2010.01.017","article-title":"A new method to isolate microglia from adult mice and culture them for an extended period of time","volume":"187","author":"Moussaud","year":"2010","journal-title":"J Neurosci Methods"},{"key":"2020042911360178800_awy077-B81","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/j.neurobiolaging.2009.10.016","article-title":"Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation","volume":"32","author":"Mutez","year":"2011","journal-title":"Neurobiol Aging"},{"key":"2020042911360178800_awy077-B82","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.4049\/jimmunol.169.6.3370","article-title":"Endotoxemia prevents the cerebral inflammatory wave induced by intraparenchymal lipopolysaccharide injection: role of glucocorticoids and CD14","volume":"169","author":"Nadeau","year":"2002","journal-title":"J Immunol"},{"key":"2020042911360178800_awy077-B83","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1089\/089771501750451857","article-title":"IL-1 Receptor antagonist prevents apoptosis and caspase-3 activation after spinal cord injury","volume":"18","author":"Nesic","year":"2001","journal-title":"J Neurotrauma"},{"key":"2020042911360178800_awy077-B84","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/BJ20100483","article-title":"14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization","volume":"430","author":"Nichols","year":"2010","journal-title":"Biochem J"},{"key":"2020042911360178800_awy077-B85","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMc055509","article-title":"LRRK2 G2019S as a cause of Parkinson\u2019s disease in Ashkenazi Jews","volume":"354","author":"Ozelius","year":"2006","journal-title":"N Engl J Med"},{"key":"2020042911360178800_awy077-B86","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.2174\/138161211798220918","article-title":"Cytokine signaling modulates blood-brain barrier function","volume":"17","author":"Pan","year":"2011","journal-title":"Curr Pharm Des"},{"key":"2020042911360178800_awy077-B87","first-page":"R52","article-title":"Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice","volume":"276","author":"Paul","year":"1999","journal-title":"Am J Physiol"},{"key":"2020042911360178800_awy077-B88","volume-title":"The mouse brain in stereotaxic coordinates","author":"Paxinos","year":"2001"},{"issue":"Pt 7","key":"2020042911360178800_awy077-B89","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1093\/brain\/awn101","article-title":"Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease","volume":"131","author":"Pott Godoy","year":"2008","journal-title":"Brain"},{"key":"2020042911360178800_awy077-B90","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1523\/JNEUROSCI.0650-14.2015","article-title":"Leucine-rich repeat kinase 2 modulates neuroinflammation and neurotoxicity in models of human immunodeficiency virus 1-associated neurocognitive disorders","volume":"35","author":"Puccini","year":"2015","journal-title":"J Neurosci"},{"key":"2020042911360178800_awy077-B91","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.parkreldis.2011.11.019","article-title":"First neuropathological description of a patient with Parkinson's disease and LRRK2 p.N1437H mutation","volume":"18","author":"Puschmann","year":"2012","journal-title":"Parkinsonism Relat Disord"},{"key":"2020042911360178800_awy077-B92","doi-asserted-by":"crossref","first-page":"e18568","DOI":"10.1371\/journal.pone.0018568","article-title":"Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2","volume":"6","author":"Ramonet","year":"2011","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B93","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1600-0404.2007.00894.x","article-title":"Circulating interleukin-15 and RANTES chemokine in Parkinson's disease","volume":"116","author":"Rentzos","year":"2007","journal-title":"Acta Neurol Scand"},{"key":"2020042911360178800_awy077-B94","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0006-8993(99)02189-7","article-title":"Brain endothelial cell production of a neuroprotective cytokine, interleukin-6, in response to noxious stimuli","volume":"851","author":"Reyes","year":"1999","journal-title":"Brain Res"},{"key":"2020042911360178800_awy077-B95","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/j.1749-6632.1997.tb51775.x","article-title":"Endotoxin shock-associated hypothermia","volume":"813","author":"Romanovsky","year":"1997","journal-title":"Ann N Y Acad Sci"},{"key":"2020042911360178800_awy077-B96","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S1474-4422(11)70175-2","article-title":"Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case\u2013control study","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol"},{"key":"2020042911360178800_awy077-B97","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12974-015-0449-7","article-title":"Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-kappaB p50 signaling in cultured microglia cells","volume":"12","author":"Russo","year":"2015","journal-title":"J Neuroinflammation"},{"key":"2020042911360178800_awy077-B98","doi-asserted-by":"crossref","first-page":"e94826","DOI":"10.1371\/journal.pone.0094826","article-title":"Unaltered striatal dopamine release levels in young Parkin knockout, Pink1 knockout, DJ-1 knockout and LRRK2 R1441G transgenic mice","volume":"9","author":"Sanchez","year":"2014","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B99","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/ng.485","article-title":"Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease","volume":"41","author":"Satake","year":"2009","journal-title":"Nat Genet"},{"key":"2020042911360178800_awy077-B100","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1471-4159.2009.05984.x","article-title":"Differential gene expression in LPS\/IFNgamma activated microglia and macrophages: in vitro versus in vivo","volume":"109","author":"Schmid","year":"2009","journal-title":"J Neurochem"},{"key":"2020042911360178800_awy077-B101","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00213-013-3180-z","article-title":"FACS analysis of neuronal-glial interactions in the nucleus accumbens following morphine administration","volume":"230","author":"Schwarz","year":"2013","journal-title":"Psychopharmacology"},{"key":"2020042911360178800_awy077-B102","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1038\/nn.4160","article-title":"Cell type- and brain region-resolved mouse brain proteome","volume":"18","author":"Sharma","year":"2015","journal-title":"Nat Neurosci"},{"key":"2020042911360178800_awy077-B103","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1365-2990.2011.01187.x","article-title":"LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study","volume":"37","author":"Sharma","year":"2011","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2020042911360178800_awy077-B104","doi-asserted-by":"crossref","first-page":"164ra161","DOI":"10.1126\/scitranslmed.3004485","article-title":"Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations","volume":"4","author":"Sheng","year":"2012","journal-title":"Sci Transl Med"},{"key":"2020042911360178800_awy077-B105","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1523\/JNEUROSCI.2712-13.2014","article-title":"Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies","volume":"34","author":"Skibinski","year":"2014","journal-title":"J Neurosci"},{"key":"2020042911360178800_awy077-B106","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/nn1776","article-title":"Kinase activity of mutant LRRK2 mediates neuronal toxicity","volume":"9","author":"Smith","year":"2006","journal-title":"Nat Neurosci"},{"key":"2020042911360178800_awy077-B107","doi-asserted-by":"crossref","first-page":"e12813","DOI":"10.7554\/eLife.12813","article-title":"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases","volume":"5","author":"Steger","year":"2016","journal-title":"Elife"},{"key":"2020042911360178800_awy077-B108","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.immuni.2017.02.010","article-title":"Integrative proteomics and phosphoproteomics profiling reveals dynamic signaling networks and bioenergetics pathways underlying T cell activation","volume":"46","author":"Tan","year":"2017","journal-title":"Immunity"},{"key":"2020042911360178800_awy077-B109","doi-asserted-by":"crossref","first-page":"e21519","DOI":"10.1371\/journal.pone.0021519","article-title":"Regulation of LRRK2 expression points to a functional role in human monocyte maturation","volume":"6","author":"Thevenet","year":"2011","journal-title":"PLoS One"},{"key":"2020042911360178800_awy077-B110","doi-asserted-by":"crossref","first-page":"14622","DOI":"10.1073\/pnas.0906334106","article-title":"R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice","volume":"106","author":"Tong","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020042911360178800_awy077-B111","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1096\/fasebj.10.2.8641570","article-title":"Interleukin-1 receptors on rat brain endothelial cells: a role in neuroimmune interaction?","volume":"10","author":"Van Dam","year":"1996","journal-title":"FASEB J"},{"key":"2020042911360178800_awy077-B112","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbi.2005.10.005","article-title":"Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide","volume":"20","author":"Verma","year":"2006","journal-title":"Brain Behav Immun"},{"key":"2020042911360178800_awy077-B113","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1002\/cne.23583","article-title":"Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents","volume":"522","author":"West","year":"2014","journal-title":"J Comp Neurol"},{"key":"2020042911360178800_awy077-B114","doi-asserted-by":"crossref","first-page":"16842","DOI":"10.1073\/pnas.0507360102","article-title":"Parkinson\u2019s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity","volume":"102","author":"West","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020042911360178800_awy077-B115","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/hmg\/ddl471","article-title":"Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity","volume":"16","author":"West","year":"2007","journal-title":"Hum Mol Genet"},{"key":"2020042911360178800_awy077-B116","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.neuroscience.2007.10.062","article-title":"Developmental regulation of leucine-rich repeat kinase 1 and 2 expression in the brain and other rodent and human organs: implications for Parkinson's disease","volume":"152","author":"Westerlund","year":"2008","journal-title":"Neuroscience"},{"key":"2020042911360178800_awy077-B117","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000289232","article-title":"Leucine-rich repeat kinase 2 gene-associated disease: redefining genotype-phenotype correlation","volume":"7","author":"Wider","year":"2010","journal-title":"Neurodegener Dis"},{"key":"2020042911360178800_awy077-B118","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/mds.24924","article-title":"Identical twins with Leucine rich repeat kinase type 2 mutations discordant for Parkinson's disease","volume":"27","author":"Xiromerisiou","year":"2012","journal-title":"Mov Disord"},{"key":"2020042911360178800_awy077-B119","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.nbd.2015.02.031","article-title":"Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice","volume":"78","author":"Yue","year":"2015","journal-title":"Neurobiol Dis"},{"key":"2020042911360178800_awy077-B120","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1056\/NEJMoa0903753","article-title":"Genome wide association study of leprosy","volume":"361","author":"Zhang","year":"2009","journal-title":"N Engl J Med"},{"key":"2020042911360178800_awy077-B121","doi-asserted-by":"crossref","first-page":"8103","DOI":"10.4049\/jimmunol.177.11.8103","article-title":"A requirement for microglial TLR4 in leukocyte recruitment into brain in response to lipopolysaccharide","volume":"177","author":"Zhou","year":"2006","journal-title":"J Immunol"},{"key":"2020042911360178800_awy077-B122","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","article-title":"Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology","volume":"44","author":"Zimprich","year":"2004","journal-title":"Neuron"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/141\/6\/1753\/33142473\/awy077.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/141\/6\/1753\/33142473\/awy077.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T12:03:58Z","timestamp":1588161838000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/141\/6\/1753\/4944716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,21]]},"references-count":122,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,3,21]]},"published-print":{"date-parts":[[2018,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awy077","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,6]]},"published":{"date-parts":[[2018,3,21]]}}}