{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:46:05Z","timestamp":1759970765462,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20303","D202302089587","2022XKQ0205"],"award-info":[{"award-number":["U22A20303","D202302089587","2022XKQ0205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Project of Hunan Provincial Health Commission","award":["U22A20303","D202302089587","2022XKQ0205"],"award-info":[{"award-number":["U22A20303","D202302089587","2022XKQ0205"]}]},{"name":"Hunan Province Developmental Biology and Biological Breeding Key Programs","award":["U22A20303","D202302089587","2022XKQ0205"],"award-info":[{"award-number":["U22A20303","D202302089587","2022XKQ0205"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acidosis, a common feature of cerebral ischemia and hypoxia, results in neuronal damage and death. This study aimed to investigate the protective effects and mechanisms of action of melatonin against acidosis-induced neuronal damage. SH-SY5Y cells were exposed to an acidic environment to simulate acidosis, and a photothrombotic (PT) infarction model was used to establish an animal model of cerebral ischemia of male C57\/BL6J mice. Both in vivo and in vitro studies demonstrated that acidosis increased cytoplasmic transcription factor EB (TFEB) levels, reduced nuclear TFEB levels, and suppressed autophagy, as evidenced by elevated p62 levels, a higher LC3-II\/LC3-I ratio, decreased synapse-associated proteins (PSD-95 and synaptophysin), and increased neuronal apoptosis. In contrast, melatonin promoted the nuclear translocation of TFEB, enhanced autophagy, and reversed neuronal apoptosis. Moreover, the role of TFEB in melatonin\u2019s neuroprotective effects was validated by modulating TFEB nuclear translocation. In conclusion, melatonin mitigates acidosis-induced neuronal damage by promoting the nuclear translocation of TFEB, thereby enhancing autophagy. These findings offer new insights into potential treatments for acidosis.<\/jats:p>","DOI":"10.3390\/ijms26031170","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T10:36:28Z","timestamp":1738146988000},"page":"1170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Mitigates Acidosis-Induced Neuronal Damage by Up-Regulating Autophagy via the Transcription Factor EB"],"prefix":"10.3390","volume":"26","author":[{"given":"Yan","family":"Shi","sequence":"first","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharamceutical Sciences, Health Science Center, Hunan Normal University, Changsha 410013, China"},{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"},{"name":"Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyu","family":"Mi","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoxue","family":"Gan","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shishan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharamceutical Sciences, Health Science Center, Hunan Normal University, Changsha 410013, China"},{"name":"School of Medical Technology and Translational Medicine, Hunan Normal University, Changsha 410006, China"},{"name":"Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"T\u00f3th, O.M., Menyh\u00e1rt, \u00c1., Frank, R., Hantosi, D., Farkas, E., and Bari, F. 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