{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:08:14Z","timestamp":1789103294862,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"9","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":[{"name":"Science and Technology Program of XPCC","award":["2024ZD025"],"award-info":[{"award-number":["2024ZD025"]}]},{"name":"Science and Technology Program of XPCC","award":["2025DB010"],"award-info":[{"award-number":["2025DB010"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82360671"],"award-info":[{"award-number":["82360671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82360671"],"award-info":[{"award-number":["82360671"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shihezi University International Science and Technology Cooperation Promotion Programme Project","award":["GJHZ202308"],"award-info":[{"award-number":["GJHZ202308"]}]},{"award":["GJHZ202308"],"award-info":[{"award-number":["GJHZ202308"]}],"id":[{"id":"https:\/\/ror.org\/04x0kvm78","id-type":"ROR","asserted-by":"publisher"}]},{"name":"2024 Seventh Division Huyanghe City Fiscal Science and Technology Project","award":["2024A15"],"award-info":[{"award-number":["2024A15"]}]},{"name":"Tianshan Young Talent Scientific and Technological Innovation Team: Innovative Team for Research on Prevention and Treatment of High-incidence Diseases in Central Asia","award":["2023TSYCTD0020"],"award-info":[{"award-number":["2023TSYCTD0020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Long-term exposure to polystyrene nanoplastics (PS-NPs) causes neurotoxicity, but the underlying mechanisms remain unclear. We combined network toxicology, molecular docking, and in vivo experiments to investigate the role of MTOR-TFEB-regulated autophagy in PS-NP-induced neurotoxicity. Potential targets related to PS-NPs and neurodegenerative diseases were screened from public databases. Enrichment analysis indicated involvement of neurodegenerative and autophagy pathways. Protein\u2013protein interaction and docking simulations prioritized MTOR as a candidate target. Sprague\u2013Dawley rats were gavaged with PS-NPs (0.15 or 1.5 mg\/kg) for 60 days. Morris water maze tests showed impaired spatial learning and memory. Western blotting of hippocampal tissues revealed increased p-MTOR\/MTOR ratios, decreased total cytoplasmic and nuclear TFEB, reduced lysosomal proteins (LAMP2, CTSD, and CTSB), elevated autophagy markers SQSTM1 and MAP1LC3B-II, and altered apoptosis regulators (BAX up and BCL2 down). Collectively, PS-NPs disrupt the MTOR-TFEB axis, impair lysosomal function and autophagic clearance, and promote apoptosis, leading to neurocognitive deficits. These findings provide mechanistic insights into the MTOR-TFEB axis and highlight it as a candidate pathway warranting further evaluation as a potential intervention target.<\/jats:p>","DOI":"10.3390\/toxics14090801","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:02:48Z","timestamp":1788962568000},"page":"801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Toxicology Integrates In Vivo Evidence Linking Impaired Autophagic Clearance Involving the MTOR-TFEB Axis to Polystyrene Nanoplastic-Induced Neurotoxicity"],"prefix":"10.3390","volume":"14","author":[{"given":"Na","family":"Tang","sequence":"first","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Yajie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3465-9789","authenticated-orcid":false,"given":"Qiang","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Public Health, Shihezi University, Shihezi 832000, China"},{"name":"Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"conceptualization","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","first-page":"133339","DOI":"10.1016\/j.jhazmat.2023.133339","article-title":"Continuous Generation and Release of Microplastics and Nanoplastics from Polystyrene by Plastic-Degrading Marine Bacteria","volume":"465","author":"Lv","year":"2024","journal-title":"J. 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