{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:41:28Z","timestamp":1788518488257,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"published-print":{"date-parts":[[2023,9,12]]},"abstract":"<jats:p>Increasing evidence highlights that excessive iron accumulation in the brain plays a vital role in neuronal senescence and is implicated in the pathogenesis of age-related neurodegenerative diseases, including Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD). Therefore, the chemical compounds that eliminate an iron overload may provide better protection against oxidative stress conditions that cause the accumulation of senescent cells during brain aging. Ebselen has been identified as a strongly useful compound in the research on redox biology mechanisms. We hypothesized that ebselen could alleviate an iron overload-induced oxidative stress and consequently reverses the senescence-like phenotypes in the neuronal cells. In the present study, SH-SY5Y cells were treated with ferric ammonium citrate (FAC) before ebselen, and the evaluation of the cellular iron homeostasis, the indicators of oxidative stress, and the onset of senescence phenotypes and mechanisms were carried out accordingly. Our findings showed that ebselen ameliorated the FAC-mediated iron overload by decreasing the expression of divalent metal transporter 1 (DMT1) and ferritin light chain (FT-L) proteins. In contrast, it increased the expression of ferroportin 1 (FPN1) protein and its correlation led to a decrease in the expression of the cytosolic labile iron pool (LIP). Furthermore, ebselen significantly reduced reactive oxygen species (ROS) and rescued the mitochondrial membrane potential (\u0394\u03a8m). Notably, ebselen restored the biomarkers of cellular senescence by reducing the number of senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) positive cells and senescence-associated secretory phenotypes (SASP). This also suppressed the expression of p53 protein targeting DNA damage response (DDR)\/p21 cyclin-dependent kinase (CDK) inhibitor through a mTORC1 signaling pathway. Potentially, ebselen could be a therapeutic agent for treating brain aging and AD by mitigating iron accumulation and restoring senescence in SH-SY5Y cells.<\/jats:p>","DOI":"10.1155\/2023\/6641347","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T16:05:09Z","timestamp":1694534709000},"page":"1-11","source":"Crossref","is-referenced-by-count":6,"title":["Ebselen, Iron Uptake Inhibitor, Alleviates Iron Overload-Induced Senescence-Like Neuronal Cells SH-SY5Y via Suppressing the mTORC1 Signaling Pathway"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3292-1851","authenticated-orcid":true,"given":"Sirirak","family":"Mukem","sequence":"first","affiliation":[{"name":"School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9200-8525","authenticated-orcid":true,"given":"Ibrahim","family":"Sayoh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Science and Technology, Princess of Naradhiwas University, Narathiwat 96000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8221-9454","authenticated-orcid":true,"given":"Saowanee","family":"Maungchanburi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-8477","authenticated-orcid":true,"given":"Tipsuda","family":"Thongbuakaew","sequence":"additional","affiliation":[{"name":"School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(14)70117-6"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1771-4"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2018.02.010"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00019"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-018-0126-2"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2021.11.003"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2009.05.004"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12061289"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.324847"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.035"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00173"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.17196.1"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1159\/000484629"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1366-5"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1094351"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00416-y"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.645593"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.005"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.03.010"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-018-9767-3"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2016.00208"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1159\/000447841"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.08.015"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(84)90083-2"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.05.029"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.343"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2018.11.021"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2006.08.005"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.05.016"},{"issue":"8","key":"30","first-page":"7907","article-title":"DMT1 inhibitor ebselen inhibits iron-induced amyloidogenic APP processing","volume":"11","author":"L. Xie","year":"2018","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1997.2126"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e07310"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000167rr"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1042\/bj20061840"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.3390\/cells8020198"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.01.012"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.7554\/elife.73456"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14567"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2009.03.002"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144230"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2021.14"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2019-0218"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.3233\/jad-180317"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00954-y"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-017-1463-2"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114312"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01111-9"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.966478"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3262-17.2018"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107886"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122579"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101462r"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.09.002"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1172\/jci158447"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00870.x"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1038\/nature13148"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10308"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00483-8"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00321"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005741"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-016-0474-7"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.05.081"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030420"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3225"}],"container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/aps\/2023\/6641347.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/aps\/2023\/6641347.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/aps\/2023\/6641347.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T16:05:13Z","timestamp":1694534713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/aps\/2023\/6641347\/"}},"subtitle":[],"editor":[{"given":"Kim Wei","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":64,"alternative-id":["6641347","6641347"],"URL":"https:\/\/doi.org\/10.1155\/2023\/6641347","relation":{},"ISSN":["2633-4690","2633-4682"],"issn-type":[{"value":"2633-4690","type":"electronic"},{"value":"2633-4682","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9,12]]}}}