{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:55:17Z","timestamp":1790225717221,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T00:00:00Z","timestamp":1534032000000},"content-version":"vor","delay-in-days":223,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700070"],"award-info":[{"award-number":["81700070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>The present study investigated the nuclear factor erythroid 2\u2010related factor 2\u2010 (Nrf2\u2010) antioxidant response element (ARE) signaling pathway in patients with moderate to severe obstructive sleep apnea\u2010hypopnea syndrome (OSAHS). Their correlation with neurocognitive impairment metrics was investigated to explore potential pathogenesis in OSAHS. Forty\u2010eight patients with OSAHS and 28 controls underwent testing with the Epworth Sleep Scale (ESS), MATRICS Consensus Cognitive Battery (MCCB), Stroop Color and Word Test, polysomnography (PSG), and measurements of the concentration of plasma superoxide dismutase (SOD) and thioredoxin (Trx). Further, 20 pairs of matched patients with OSAHS and controls were selected for measurement of the expression (protein and mRNA) of Nrf2 and of its downstream antioxidase, heme oxygenase\u20101 (HO\u20101), in peripheral mononuclear cells (PBMCs). Finally, correlations between neurocognitive impairment and the above metrics were analyzed. Expression of Nrf2 and HO\u20101 mRNA and protein in the PBMCs, as well as plasma SOD and Trx levels, were significantly reduced in patients with OSAHS. After adjusting for education, sex, age, and smoking index, the expression of Nrf2\u2010ARE signaling pathway proteins (or mRNA) was closely correlated with sleep respiratory parameters. An inverse relationship was demonstrated between the expression of nuclear Nrf2 in PBMCs, concentration of plasma SOD and Trx, and apnea\u2010hypopnea index (AHI) in patients with OSAHS. Trx, nuclear Nrf2 protein, and HO\u20101 protein were also negatively correlated with the percent of time that SaO<jats:sub>2<\/jats:sub> was less than 90% (TSat90). Total Nrf2 protein level was positively correlated with AHI and TSat90 and negatively correlated with minimum SaO<jats:sub>2<\/jats:sub> (LSaO<jats:sub>2<\/jats:sub>), while nuclear Nrf2 protein and HO\u20101 protein were positively correlated with LSaO<jats:sub>2<\/jats:sub>. Moreover, significant positive correlations were found between maze scores and expression of nuclear Nrf2 protein, HO\u20101 protein, and SOD and Trx levels. Furthermore, inverse relationships between total Nrf2 protein in PBMCs and HVLT\u2010R and maze scores were found. Multiple linear regression showed plasma Trx concentration as a potential predictor of maze and BVMT\u2010R scores. In conclusion, the expression of Nrf2\u2010ARE molecules and related antioxidases is significantly decreased in patients with OSAHS and is correlated with neurocognitive dysfunction. The Nrf2\u2010ARE signaling pathway may play a crucial role in neurocognitive impairment in patients with moderate to severe OSAHS. Further studies are needed to explore the exact mechanisms and potential treatment interventions.<\/jats:p>","DOI":"10.1155\/2018\/3529709","type":"journal-article","created":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T23:31:06Z","timestamp":1534116666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Dysfunction of Nrf2\u2010ARE Signaling Pathway: Potential Pathogenesis in the Development of Neurocognitive Impairment in Patients with Moderate to Severe Obstructive Sleep Apnea\u2010Hypopnea 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