{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:24:34Z","timestamp":1793388274396,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mitochondrial dysfunction has been suggested to play an important role in all stages of multiple sclerosis (MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the expression of two mitophagy-related proteins, PTEN-induced kinase 1 (PINK1) and PARKIN, in a cohort of Japanese patients with different neuroinflammatory disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Protein concentrations were measured using commercial ELISA in paired cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), and from age- and sex-matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CSF and serum concentrations of PINK1 were higher in patients with MS than in patients with NMOSD (<jats:italic>p<\/jats:italic> = 0.004 and <jats:italic>p<\/jats:italic> &amp;lt; 0.001, respectively), MOGAD (<jats:italic>p<\/jats:italic> = 0.008 and <jats:italic>p<\/jats:italic> = 0.011, respectively), and controls (<jats:italic>p<\/jats:italic> = 0.021 and <jats:italic>p<\/jats:italic> = 0.002, respectively). CSF and concentrations of PARKIN were elevated in patients with MS in comparison with those in controls (<jats:italic>p<\/jats:italic> = 0.016 and <jats:italic>p<\/jats:italic> = 0.05, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study highlighted the importance of mitophagy in MS and suggested the potential application of PINK1 and PARKIN as biomarkers to predict disease activity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.681386","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T07:54:10Z","timestamp":1628063650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Potential of PINK1 and PARKIN Proteins as Biomarkers for Active Multiple Sclerosis: A Japanese Cohort Study"],"prefix":"10.3389","volume":"12","author":[{"given":"Davide","family":"Cossu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Antonio","family":"Sechi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.168","article-title":"Progressive Multiple Sclerosis: Pathology and Pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat Rev Neurol"},{"key":"B2","unstructured":"Atlas of MS, 3rd Ed2020"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww258","article-title":"Progressive Multiple Sclerosis: From Pathogenic Mechanisms to Treatment","volume":"140","author":"Correale","year":"2017","journal-title":"Brain"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514544537","article-title":"The Central Role of Mitochondria in Axonal Degeneration in Multiple Sclerosis","volume":"20","author":"Campbell","year":"2014","journal-title":"Mult Scler"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/srep33249","article-title":"Mitochondrial Dysfunction Is an Important Cause of Neurological Deficits in an Inflammatory Model of Multiple Sclerosis","volume":"6","author":"Sadeghian","year":"2016","journal-title":"Sci Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2019.116429","article-title":"GDF-15, A Mitochondrial Disease Biomarker, Is Associated With the Severity of Multiple Sclerosis","volume":"405","author":"Nohara","year":"2019","journal-title":"J Neurol Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316234","article-title":"Autophagy and Mitophagy Elements Are Increased in Body Fluids of Multiple Sclerosis-Affected Individuals","volume":"89","author":"Patergnani","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12974-019-1526-0","article-title":"Correlation Between Auto\/Mitophagic Processes and Magnetic Resonance Imaging Activity in Multiple Sclerosis Patients","volume":"16","author":"Castellazzi","year":"2019","journal-title":"J Neuroinflamm"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/srep01002","article-title":"PINK1-Mediated Phosphorylation of the Parkin Ubiquitin-Like Domain Primes Mitochondrial Translocation of Parkin and Regulates Mitophagy","volume":"2","author":"Shiba-Fukushima","year":"2012","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-017-1742-7","article-title":"Twenty Years Since the Discovery of the Parkin Gene","volume":"124","author":"Hattori","year":"2017","journal-title":"J Neural Transm (Vienna)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24608","article-title":"Clinicopathological Features in Anterior Visual Pathway in Neuromyelitis Optica","volume":"79","author":"Hokari","year":"2016","journal-title":"Ann Neurol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","article-title":"Diagnostic Criteria for Multiple Sclerosis: 2010 Revisions to the Mcdonald Criteria","volume":"69","author":"Polman","year":"2011","journal-title":"Ann Neurol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729","article-title":"International Panel for NMO Diagnosis. 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