{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:58:19Z","timestamp":1785383899943,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C2091254"],"award-info":[{"award-number":["2022R1A2C2091254"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u201000223501"],"award-info":[{"award-number":["RS\u20102023\u201000223501"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002632","name":"Hallym University","doi-asserted-by":"publisher","award":["MHC\u2010202503\u2010005"],"award-info":[{"award-number":["MHC\u2010202503\u2010005"]}],"id":[{"id":"10.13039\/501100002632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Altered immune responses including increased neutrophils have been reported in Parkinson's disease (PD); however, the role of neutrophil extracellular traps (NETs) remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to evaluate the contribution of NETs to the systemic immunity and central nervous system (CNS) in PD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic analysis from the Parkinson's Progression Markers Initiative (PPMI) cohort was performed. Serum NETs were measured by myeloperoxidase (MPO)\u2010DNA and citrullinated histone H3 (CitH3)\u2010DNA complexes using enzyme\u2010linked immunosorbent assay (ELISA). In addition, NET structures in postmortem brains of individuals with PD and multiple system atrophy (MSA) were quantified using ELISA and visualized by confocal microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Differential expression gene analysis showed significant systemic upregulation of\n                      <jats:italic>PADI4<\/jats:italic>\n                      expression, which encodes the NET\u2010priming enzyme peptidylarginine deiminase 4, in patients with PD compared with control subjects. In the regional cross\u2010sectional cohort, serum MPO\u2010DNA complexes were reduced in patients with PD compared with control subjects and showed a graded reduction with disease severity; this reduction was independently replicated using a CitH3\u2010DNA ELISA. In contrast, NET structures were markedly increased in postmortem brain tissues from individuals with PD and MSA compared with control subjects. Confocal imaging further confirmed the presence of NETs in the PD brain cortex, with an increased density in the substantia nigra and in close proximity to Lewy bodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrated systemic priming of NET\u2010associated pathways accompanied by reduced circulating NET complexes in PD, alongside substantial NETs deposition within the CNS. Together, these observations identify the PADI4\u2010NET axis as a candidate immune feature of PD that warrants further mechanistic investigation. \u00a9 2026 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70443","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:04:11Z","timestamp":1785380651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Systemic Transcriptomic Profiling and Neuropathological Deposition of Neutrophil Extracellular Traps in Parkinson's Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-5566","authenticated-orcid":false,"given":"Huu Dat","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University  Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine  Anyang Republic of Korea"},{"name":"Hallym Neurological Institute Hallym University  Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7760-5524","authenticated-orcid":false,"given":"Seungmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology and Movement Disorder Centre Seoul National University Hospital, College of Medicine, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeo\u2010Il","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University  Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine  Anyang Republic of Korea"},{"name":"Hallym Neurological Institute Hallym University  Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-1552","authenticated-orcid":false,"given":"Yun Joong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yongin Severance Hospital Yonsei University College of Medicine  Yongin Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology and Movement Disorder Centre Seoul National University Hospital, College of Medicine, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-6569","authenticated-orcid":false,"given":"Young Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital, Hallym University  Anyang Republic of Korea"},{"name":"Laboratory of Parkinson's Disease and Neurodegenerative Disease Hallym Institute for Translational Medicine  Anyang Republic of Korea"},{"name":"Hallym Neurological Institute Hallym University  Anyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe W","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune dysfunction in Parkinson disease","volume":"22","author":"Tansey MG","year":"2022","journal-title":"Nat Rev 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