{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:31Z","timestamp":1792166311309,"version":"4.4.0"},"reference-count":114,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32302926"],"award-info":[{"award-number":["32302926"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32503297"],"award-info":[{"award-number":["32503297"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32473083"],"award-info":[{"award-number":["32473083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006606","name":"Tianjin Natural Science Foundation","doi-asserted-by":"crossref","award":["24JCQNJC01290"],"award-info":[{"award-number":["24JCQNJC01290"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100019065","name":"Tianjin Science and Technology Planning Project","doi-asserted-by":"crossref","award":["25ZYCGSN00730"],"award-info":[{"award-number":["25ZYCGSN00730"]}],"id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The expanding application of zinc oxide nanoparticles (ZnO NPs) in consumer products, medicine, and the food industry has raised significant concerns regarding their potential neurotoxicity. This review synthesizes current understanding of the pathways by which ZnO NPs gain access to the central nervous system (CNS), their resulting neurotoxic effects, and the underlying molecular mechanisms. These nanoparticles primarily breach the CNS via translocation across the blood\u2013brain barrier, axonal transport along sensory nerves, and disruption of the microbiota\u2013gut\u2013brain axis. Upon entry, ZnO NPs induce behavioral deficits, including impaired learning, memory, and motor function, alongside pathological brain damage. The neurotoxicity is driven by a multi-faceted mechanism involving mitochondrial dysfunction, oxidative stress, energy depletion, and neuroinflammation, often triggered by the release of Zn2+ ions. Furthermore, ZnO NPs can activate diverse cell death pathways, including apoptosis, ferroptosis, and pyroptosis. Critically, their neurotoxic potential is intrinsically linked to their physicochemical properties, such as size and shape. Emerging evidence also suggests that ZnO NP exposure may promote the aggregation of pathological proteins like Tau, thereby potentially increasing the risk for neurodegenerative diseases. Finally, we discuss potential mitigation strategies, such as surface modification and intervention with natural compounds. This review underscores the need for a refined risk assessment of ZnO NPs to ensure their safe deployment.<\/jats:p>","DOI":"10.3390\/toxics14010011","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:01:33Z","timestamp":1766386893000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8711-7731","authenticated-orcid":false,"given":"Chun","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No. 22, Xiqing District, Tianjin 300384, China"},{"name":"Technology Innovation Center for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyao","family":"Pei","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No. 22, Xiqing District, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonger","family":"Yu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No. 22, Xiqing District, Tianjin 300384, 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Agricultural University, Jinjing Road No. 22, Xiqing District, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No. 22, Xiqing District, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1860-3582","authenticated-orcid":false,"given":"Shusheng","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Technology Innovation Center for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, 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