{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:47:31Z","timestamp":1777434451396,"version":"3.51.4"},"reference-count":57,"publisher":"SAGE Publications","issue":"18","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Neuroinflammation and redox dysfunction are recognized factors in Parkinson's disease (PD) pathogenesis, and diabetes is implicated as a potentially predisposing condition. Remarkably, upregulation of glutaredoxin-1 (Grx1) is implicated in regulation of inflammatory responses in various disease contexts, including diabetes. In this study, we investigated the potential impact of Grx1 upregulation in the central nervous system on dopaminergic (DA) viability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Increased GLRX copy number in PD patients was associated with earlier PD onset, and Grx1 levels correlated with levels of proinflammatory tumor necrosis factor-alpha (TNF-\u03b1) in mouse and human brain samples, prompting mechanistic\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      studies. Grx1 content\/activity in microglia was upregulated by lipopolysaccharide (LPS), or TNF-\u03b1, treatment. Adenoviral overexpression of Grx1, matching the extent of induction by LPS, increased microglial activation; Grx1 silencing diminished activation. Selective inhibitors\/probes of nuclear factor \u03baB (NF-\u03baB) activation revealed\n                      <jats:italic toggle=\"yes\">glrx1<\/jats:italic>\n                      induction to be mediated by the Nurr1\/NF-\u03baB axis. Upregulation of Grx1 in microglia corresponded to increased death of neuronal cells in coculture. With a mouse diabetes model of diet-induced insulin resistance, we found upregulation of Grx1 in brain was associated with DA loss (decreased tyrosine hydroxylase [TH]; diminished TH-positive striatal axonal terminals); these effects were not seen with Grx1-knockout mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>\n                      Our results indicate that Grx1 upregulation promotes neuroinflammation and consequent neuronal cell death\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , and synergizes with proinflammatory insults to promote DA loss\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Our findings also suggest a genetic link between elevated Grx1 and PD development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      data suggest Grx1 upregulation promotes neurotoxic neuroinflammation, potentially contributing to PD.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                      . 25, 967\u2013982.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2015.6598","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T09:51:53Z","timestamp":1464169913000},"page":"967-982","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Upregulation of Glutaredoxin-1 Activates Microglia and Promotes Neurodegeneration: Implications for Parkinson's Disease"],"prefix":"10.1177","volume":"25","author":[{"given":"Olga","family":"Gorelenkova Miller","sequence":"first","affiliation":[{"name":"Case Western Reserve University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica Belle","family":"Behring","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra 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