{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:10:24Z","timestamp":1768407024997,"version":"3.49.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31300812"],"award-info":[{"award-number":["31300812"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["20180550468"],"award-info":[{"award-number":["20180550468"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Varying degrees of central nervous system neuropathy induced by diabetes mellitus (DM) contribute to a cognitive disorder known as diabetic encephalopathy (DE), which is also one of the independent risk factors for Alzheimer\u2019s disease (AD). Endoplasmic reticulum stress (ERS) plays a critical role in the occurrence and development of DE and AD. However, its molecular mechanism remains largely unknown. This study aims to investigate whether thioredoxin-1 (Trx-1) could alleviate DE and AD through ERS, oxidative stress (OS) and apoptosis signaling pathways. Mice were randomly divided into a wild-type group (WT-NC), a streptozotocin (STZ)-treated DM group (WT-DM), a Trx-1-TG group (TG-NC) and a Trx-1-TG DM group (TG-DM). Diabetic animals showed an increase in the time spent in the target quadrant and the number of platform crossings as well as AD-like behavior in the water maze experiment. The immunocontent of the AD-related protein Tau and the levels of cell apoptosis, \u03b2-amyloid (A\u03b2) plaque formation and neuronal degeneration in the hippocampus of the diabetic group were increased. Some key factors associated with ERS, such as protein disulfide isomerase (PDI), glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1\u03b1 (IRE1\u03b1), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase-1 (ASK1), c-Jun N-terminal kinase (JNK), protein kinase RNA (PKR)-like ER kinase (PERK), and C\/EBP homologous protein (CHOP), were upregulated, and other factors related to anti-oxidant stress, such as nuclear factor erythroid 2-related factor (Nrf2), were downregulated in the DM group. Moreover, DM caused an increase in the immunocontents of caspase-3 and caspase-12. However, these changes were reversed in the Trx-1-tg DM group. Therefore, we conclude that Trx-1 might be a key factor in alleviating DE and AD by regulating ERS and oxidative stress response, thus preventing apoptosis.<\/jats:p>","DOI":"10.3389\/fphys.2021.651105","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T06:20:01Z","timestamp":1621232401000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Thioredoxin-1 Is a Target to Attenuate Alzheimer-Like Pathology in Diabetic Encephalopathy by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress"],"prefix":"10.3389","volume":"12","author":[{"given":"Yu","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenghong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiying","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiying","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1038\/sj.cdd.4401818","article-title":"Involvement of glutaredoxin-1 and thioredoxin-1 in beta-amyloid toxicity and Alzheimer\u2019s disease.","volume":"13","author":"Akterin","year":"2006","journal-title":"Cell Death Differ."},{"key":"B2","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1089\/089277903322145503","article-title":"Immune response to laparoscopic bowel injury.","volume":"17","author":"Aldana","year":"2003","journal-title":"J. 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