{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T14:15:52Z","timestamp":1783174552320,"version":"3.54.6"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T00:00:00Z","timestamp":1470182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81422039"],"award-info":[{"award-number":["81422039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002865","name":"Chongqing Science and Technology Commission","doi-asserted-by":"publisher","award":["CSTC2013JCYJJQ10002"],"award-info":[{"award-number":["CSTC2013JCYJJQ10002"]}],"id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cadmium (Cd), a highly ubiquitous heavy metal, induces neurotoxicity. Melatonin, a major secretory product of the pineal gland, protects against Cd\u2010induced neurotoxicity. However, the mechanism that accounts for this protection remains to be elucidated. Herein, we exposed mouse neuroblastoma cells (Neuro\u20102a cells) to different concentrations of cadmium chloride (CdCl<jats:sub>2<\/jats:sub>) (12.5, 25, and 50\u00a0\u03bc\u00a0mol\u00a0L<jats:sup>\u22121<\/jats:sup>) for 24\u00a0hours. We showed that Cd inhibits autophagosome\u2013lysosome fusion and impairs lysosomal function, subsequently leading to nerve cell death. In addition, Cd decreases the level of transcription factor <jats:styled-content style=\"fixed-case\">EB<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">TFEB<\/jats:styled-content>) but induces the nuclear translocation of <jats:styled-content style=\"fixed-case\">TFEB<\/jats:styled-content>, associated with compromised lysosomal function or a compensatory effect after the impairment of the autophagic flux. Moreover, compared to the 50\u2010\u03bc\u00a0mol\u00a0L<jats:sup>\u22121<\/jats:sup> Cd group, administration of 1\u00a0\u03bc\u00a0mol\u00a0L<jats:sup>\u22121<\/jats:sup> melatonin increased \u201c<jats:styled-content style=\"fixed-case\">TFEB<\/jats:styled-content>\u2010responsive genes\u201d (<jats:italic>P<\/jats:italic>&lt;.05) and the levels of lysosomal\u2010associated membrane protein (0.57\u00b10.06 vs 1.00\u00b10.11, <jats:italic>P<\/jats:italic>&lt;.05), preserved lysosomal protease activity (0.52\u00b10.01 vs 0.90\u00b10.02, <jats:italic>P<\/jats:italic>&lt;.05), maintained the lysosomal <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> level (0.50\u00b10.01 vs 0.87\u00b10.05, <jats:italic>P<\/jats:italic>&lt;.01), and enhanced autophagosome\u2013lysosome fusion (0.05\u00b10.00 vs 0.21\u00b10.01, <jats:italic>P<\/jats:italic>&lt;.01). Notably, melatonin enhanced <jats:styled-content style=\"fixed-case\">TFEB<\/jats:styled-content> expression (0.37\u00b10.04 vs 0.72\u00b10.07, <jats:italic>P<\/jats:italic>&lt;.05) and nuclear translocation (2.81\u00b10.08 vs 3.82\u00b10.05, <jats:italic>P<\/jats:italic>&lt;.05). <jats:italic>Tfeb<\/jats:italic> si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> blocked the melatonin\u2010mediated elevation in autophagy\u2013lysosome machinery in Cd\u2010induced neurotoxicity (<jats:italic>P<\/jats:italic>&lt;.01). Taken together, these results uncover a potent role for <jats:styled-content style=\"fixed-case\">TFEB<\/jats:styled-content>\u2010mediated autophagy in the pathogenesis of Cd\u2010induced neurotoxicity, suggesting that control of the autophagic pathway by melatonin might provide an important clue for exploring potential targets for novel therapeutics of Cd\u2010induced neurotoxicity.<\/jats:p>","DOI":"10.1111\/jpi.12353","type":"journal-article","created":{"date-parts":[[2016,7,11]],"date-time":"2016-07-11T04:36:39Z","timestamp":1468211799000},"page":"353-369","source":"Crossref","is-referenced-by-count":82,"title":["Melatonin antagonizes cadmium\u2010induced neurotoxicity by activating the transcription factor <scp>EB<\/scp>\u2010dependent autophagy\u2013lysosome machinery in mouse neuroblastoma cells"],"prefix":"10.1111","volume":"61","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"Department of Occupational Health Third Military Medical University  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