{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:20:07Z","timestamp":1789118407990,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Science and Technology Project of Liaoning Province","doi-asserted-by":"publisher","award":["2024JH2\/102500029"],"award-info":[{"award-number":["2024JH2\/102500029"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Prolonged exposure to 1,2-dichloroethane (1,2-DCE) can lead to cognitive dysfunction, and neuronal loss is a proven key driver. In mice, 1,2-DCE exposure reduced hippocampal ATP levels, triggering AMPK phosphorylation, mTOR suppression, and ULK1 activation, along with increased Beclin 1 and LC3-II\/I levels, collectively indicating enhanced autophagy initiation. Meanwhile, p62 accumulation and decreased LAMP1 and CTSD expression indicated impaired autophagic degradation, accompanied by increased neuronal apoptosis. Consistent with these in vivo findings, PC12 cells, a neuron-like cell line, exhibited mitochondrial dysfunction after exposure to 2-chloroethanol (2-CE, a metabolite of 1,2-DCE in vivo), as evidenced by ATP depletion, mitochondrial membrane potential loss, and elevated ROS production. Furthermore, 2-CE activated the AMPK-mTOR-ULK1 signaling pathway to initiate autophagy, while also disrupting lysosomal structure and function, leading to impaired autophagic flux and enhanced apoptosis. In conclusion, prolonged 1,2-DCE exposure induces mitochondrial dysfunction and ATP depletion, activating AMPK-mTOR-ULK1-mediated autophagy initiation. Meanwhile, concomitant lysosomal damage impairs autophagic degradation, and the combined effect promotes neuronal apoptosis. These findings suggest a potential strategy for preventing and treating 1,2-DCE-induced cognitive impairment.<\/jats:p>","DOI":"10.3390\/biology15181580","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:05:43Z","timestamp":1788941143000},"page":"1580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["1,2-Dichloroethane Induces Neuronal Apoptosis Through AMPK-mTOR-ULK1 Pathway Activation and Autophagic Flux Impairment"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhenlin","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Chunting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Gaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Wanting","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang 110004, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Zijiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Liaoning Provincial Center for Disease Control and Prevention, Shenyang 110172, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Fenghong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China"},{"name":"Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jin, X., Wang, T., Liao, Y., Guo, J., Wang, G., Zhao, F., and Jin, Y. 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