{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:31:49Z","timestamp":1791167509600,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82001354"],"award-info":[{"award-number":["NSFC82001354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) lacks reliable biomarkers to predict disease trajectories or guide therapeutic strategies. Sirtuin 2 (SIRT2), a NAD+\u2010dependent deacetylase implicated in cytoskeletal destabilization and neuroinflammatory pathways in preclinical ALS models, represents a promising yet unvalidated biomarker candidate. We aimed to translate preclinical findings by validating SIRT2's role in ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross\u2010sectional cohort study was conducted, comparing serum SIRT2 levels, measured via enzyme\u2010linked immunosorbent assay (ELISA), between 182 ALS patients and 65 healthy controls. Clinical progression rates were derived from the ALS Functional Rating Scale\u2010Revised (ALSFRS\u2010R), and cognitive function was assessed using the Mini\u2013Mental State Examination (MMSE) and Edinburgh Cognitive and Behavioral ALS Screen (ECAS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SIRT2 levels were significantly elevated in ALS patients versus controls, though diagnostic accuracy was modest (AUC\u2009=\u20090.620). Furthermore, SIRT2 levels showed a weak but significant positive correlation with disease progression rate (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.182,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014) and inverse correlations with cognitive scores on both MMSE (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.250,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032) and ECAS (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.286,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031). Notably, SIRT2 demonstrated a limited but detectable ability to stratify patients into fast\u2010 and slow\u2010progressing subgroups (AUC\u2009=\u20090.635).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide preliminary clinical evidence linking elevated serum SIRT2 to disease progression and cognitive impairment in ALS, thereby supporting its role in disease heterogeneity. This work lends clinical support to preclinical insights, suggesting SIRT2 may aid in prognosis prediction and may represent a potential therapeutic target, necessitating further studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70162","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:19:16Z","timestamp":1769519956000},"page":"781-787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Serum\n                    <scp>SIRT2<\/scp>\n                    Is Associated With Rapid Progression and Cognitive Impairment in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3634-9584","authenticated-orcid":false,"given":"Jun","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianrui","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninglu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Nursing and Rehabilitation, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangwu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Research Institute of Neuromuscular and Neurodegenerative Disease Shandong University  Jinan China"},{"name":"School of Nursing and Rehabilitation, Cheeloo College of Medicine Shandong University  Jinan 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