{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:21:03Z","timestamp":1780503663133,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS)","doi-asserted-by":"publisher","award":["KAKENHI KIBAN (B) 21H02645"],"award-info":[{"award-number":["KAKENHI KIBAN (B) 21H02645"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder caused by oxidative stress-dependent loss of dopaminergic neurons in the substantia nigra and elevated microglial inflammatory responses. Recent studies show that cell loss also occurs in the hypothalamus in PD. However, effective treatments for the disorder are lacking. Thioredoxin is the major protein disulfide reductase in vivo. We previously synthesized an albumin\u2013thioredoxin fusion protein (Alb\u2013Trx), which has a longer plasma half-life than thioredoxin, and reported its effectiveness in the treatment of respiratory and renal diseases. Moreover, we reported that the fusion protein inhibits trace metal-dependent cell death in cerebrovascular dementia. Here, we investigated the effectiveness of Alb\u2013Trx against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. Alb\u2013Trx significantly inhibited 6-OHDA-induced neuronal cell death and the integrated stress response. Alb\u2013Trx also markedly inhibited 6-OHDA-induced reactive oxygen species (ROS) production, at a concentration similar to that inhibiting cell death. Exposure to 6-OHDA perturbed the mitogen-activated protein kinase pathway, with increased phosphorylated Jun N-terminal kinase and decreased phosphorylated extracellular signal-regulated kinase levels. Alb\u2013Trx pretreatment ameliorated these changes. Furthermore, Alb\u2013Trx suppressed 6-OHDA-induced neuroinflammatory responses by inhibiting NF-\u03baB activation. These findings suggest that Alb\u2013Trx reduces neuronal cell death and neuroinflammatory responses by ameliorating ROS-mediated disruptions in intracellular signaling pathways. Thus, Alb\u2013Trx may have potential as a novel therapeutic agent for PD.<\/jats:p>","DOI":"10.3390\/ijms24119758","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T02:57:30Z","timestamp":1686020250000},"page":"9758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effectiveness of Albumin-Fused Thioredoxin against 6-Hydroxydopamine-Induced Neurotoxicity In Vitro"],"prefix":"10.3390","volume":"24","author":[{"given":"Okina","family":"Sakakibara","sequence":"first","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youichirou","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kochi Medical School, Kochi University, Kohasu, Okoh-cho, Nankoku 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-3050","authenticated-orcid":false,"given":"Mayumi","family":"Ikeda-Imafuku","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichiban-Cho, Wakayama 640-8156, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-3722","authenticated-orcid":false,"given":"Yu","family":"Ishima","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-4235","authenticated-orcid":false,"given":"Masahiro","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-0751","authenticated-orcid":false,"given":"Ken-ichiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1212\/WNL.0000000000002461","article-title":"Age at onset and Parkinson disease phenotype","volume":"86","author":"Pagano","year":"2016","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Stoker, T.B., and Greenland, J.C. 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