{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:55:34Z","timestamp":1774619734105,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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\n\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01h0zpd94","doi-asserted-by":"publisher","award":["22177143"],"award-info":[{"award-number":["22177143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Inhibition of inflammation and oxidative stress is increasingly recognized as a promising therapeutic strategy for neurodegenerative diseases. In this study, we isolated two new dimeric naphtho-\u03b3-pyrone (aS)-fonsecinones B and D (1 and 2) and 14 known compounds (3\u201316) from the deep-sea-derived fungus Aspergillus niger 3A00562. Their structures were unambiguously determined through integrated physicochemical and spectroscopic analyses. Screening for neuroinflammatory inhibitors using a BV2 microglial cell model identified TMC 256 A1 (10) as the most potent candidate. Compound 10 significantly suppressed LPS-induced inflammation in BV2 cells without cytotoxicity. It concurrently inhibited LPS-triggered ROS overproduction and neutrophilic infiltration in zebrafish. Subsequent proteomics revealed that 10 targets NOS2 to modulate Alzheimer\u2019s disease (AD)-associated pathways and the KEAP1-NRF2 axis. Molecular docking and dynamics simulations demonstrated that 10 occupies the NOS2 heme-binding pocket, thereby preventing dimerization and inhibiting enzymatic activity. Finally, 10 ameliorated locomotor deficits in an AD zebrafish model. Collectively, these findings highlight compound 10 as a candidate compound for preventing inflammatory and oxidative stress damage during treatment of neurodegenerative diseases, particularly AD.<\/jats:p>","DOI":"10.3390\/md24040125","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Neuroinflammatory Naphtho-\u03b3-Pyrones from a Deep-Sea-Derived Fungus Aspergillus niger 3A00562"],"prefix":"10.3390","volume":"24","author":[{"given":"Zi-Han","family":"Xu","sequence":"first","affiliation":[{"name":"Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, China"},{"name":"School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, 3 Xueyuan Road, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng-Biao","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, 3 Xueyuan Road, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Xiu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, 3 Xueyuan Road, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, 3 Xueyuan Road, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4967-0844","authenticated-orcid":false,"given":"Xian-Wen","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, 3 Xueyuan Road, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-4969","authenticated-orcid":false,"given":"Jun-Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"572090","DOI":"10.3389\/fnagi.2020.572090","article-title":"Aging and neurodegenerative disease: Is the adaptive immune system a friend or foe? 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