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Selenoprotein W (SELENOW), known for its high selenium sensitivity and redox\u2010regulatory functions, has an unclear role in the PD\u2010related nigrostriatal pathway. In this study, we first observed that whole\u2010brain SELENOW knockout mice displayed increased vulnerability to 6\u2010hydroxydopamine (6\u2010OHDA)\u2010induced PD modeling. To investigate this further, we generated mice with dopaminergic neuron\u2010specific SELENOW knockout. While SELENOW deficiency in these neurons did not influence overall growth or baseline motor behaviors, it led to worsened motor dysfunction and increased loss of nigrostriatal dopaminergic neurons following unilateral intrastriatal 6\u2010OHDA injection. Moreover, we observed that SELENOW expression was downregulated under PD conditions. Mechanistically, this heightened susceptibility appeared linked to increased nigral oxidative stress, a weakened response of the antioxidant regulator NRF2, and diminished activation of the striatal AKT signaling pathway. In conclusion, the present study identifies SELENOW as an important modulator of dopaminergic neuron vulnerability to PD, likely through NRF2\u2010mediated redox and stress\u2010responsive signaling. These findings offer new insights into the role of selenoproteins in PD and suggest potential clues for therapeutic strategies.<\/jats:p>","DOI":"10.1096\/fj.202603178r","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:32:12Z","timestamp":1791469932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selenoprotein W Mitigates 6\u2010\n                    <scp>OHDA<\/scp>\n                    \u2010Induced Dopaminergic Damage and Motor Dysfunction in Mice"],"prefix":"10.1096","volume":"40","author":[{"given":"Hong\u2010Yang","family":"Kan","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Geriatric Neurology The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Institute of Nutrition and Diseases and Center for Research, School of Public Health Wenzhou Medical University 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