{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:16:50Z","timestamp":1780669010579,"version":"3.54.1"},"reference-count":57,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2022R1A2C1006085"],"award-info":[{"award-number":["2022R1A2C1006085"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a well-known glycolytic enzyme that plays multiple roles in energy metabolism, cell growth, and cell death, and functions as a housekeeping protein. GAPDH has been identified as a potential target of citrullination, a calcium-dependent post-translational modification mediated by peptidylarginine deiminase (PAD), in which arginine residues are converted to citrulline. This modification has been implicated in various human pathologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the function and pathological relevance of citrullinated GAPDH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated mouse monoclonal antibodies (mAbs) specific to citrullinated GAPDH and applied them in both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      systems and prion disease models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Citrullination of GAPDH at residues R200 and R248 was markedly increased in the brains of 22L scrapie-infected mice and sporadic Creutzfeldt\u2013Jakob disease patients. Both full-length GAPDH and its fragments (\u223c25\u2005kDa) were heavily citrullinated and highly expressed in neurons including Purkinje cells, astrocytes, and in plaque-like formation. In PAD2-expressing neuronal and astrocyte cell lines, citrullinated GAPDH predominantly accumulated in the nucleus and cytoplasm, with cell type-specific distribution patterns. Citrullinated GAPDH existed as both monomers and reversible oligomers, and citrullination did not alter its enzymatic activity. Immunoprecipitation demonstrated that GAPDH containing citrullinated forms interacts with prion protein. Tandem mass spectrometry analysis revealed that all arginine residues in GAPDH can be citrullinated by PAD2\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Interestingly, several asparagine and glutamine residues underwent deamidation during citrullination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that post-translationally citrullinated GAPDH serve as a potential molecular signature of neurodegeneration, which could be easily assessed by newly generated mAbs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251389157","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T19:19:38Z","timestamp":1761333578000},"page":"1520-1536","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["GAPDH citrullination as a molecular signature of neurodegeneration, assessed in prion diseases"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-2755","authenticated-orcid":false,"given":"Byungki","family":"Jang","sequence":"first","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-8814","authenticated-orcid":false,"given":"Mo-Jong","family":"Kim","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9758-3053","authenticated-orcid":false,"given":"Heewoo","family":"Choi","sequence":"additional","affiliation":[{"name":"Ilsong Institute of Life Science, Hallym University, Seoul, Republic of 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