{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T08:12:58Z","timestamp":1778227978735,"version":"3.51.4"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["2022YFC3501904"],"award-info":[{"award-number":["2022YFC3501904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374043, U23A20505"],"award-info":[{"award-number":["82374043, U23A20505"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>\n                    Parkinson\u2019s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, accompanied by oxidative stress and neuroinflammation. While nervonic acid (NA) is recognized as an essential component of myelin sphingolipids, its specific therapeutic mechanisms in PD have not been thoroughly elucidated. In this study, we investigated the neuroprotective potential of NA derived from\n                    <jats:italic toggle=\"yes\">Malania oleifera<\/jats:italic>\n                    and elucidated its underlying multimechanistic effect. We demonstrated that NA targets the core drivers of neuronal injury by restoring PTEN-induced kinase 1\u2013Parkin-mediated mitophagy to alleviate mitochondrial dysfunction and oxidative stress. Concurrently, NA reprograms microglia from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, thereby inhibiting cytokine secretion and resolving neuroinflammation. Beyond these central protective effects, metabolomics analysis revealed that NA serves as a direct biosynthetic precursor for long-chain ceramides, facilitating myelin regeneration. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice, these synergistic mechanisms collectively preserved dopaminergic neurons and improved motor function substantially. Furthermore, 16S ribosomal RNA amplicon sequencing revealed an associative remodeling of the gut microbiota, specifically enriching beneficial genera such as\n                    <jats:italic toggle=\"yes\">Akkermansia<\/jats:italic>\n                    . Collectively, this study establishes NA as a potent multitarget therapeutic that concurrently regulates oxidative stress, neuroinflammation, and myelin regeneration to alleviate PD pathology.\n                  <\/jats:p>","DOI":"10.34133\/bmr.0349","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T08:17:27Z","timestamp":1775809047000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Nervonic Acid from\n                    <i>Malania oleifera<\/i>\n                    Reverses Parkinson\u2019s Disease by Regulating Oxidative Stress, Neuroinflammation, and Gut Microbiota"],"prefix":"10.34133","volume":"30","author":[{"given":"Yuwen","family":"Li","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, \rZhejiang University, Hangzhou 310058, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Peng","sequence":"additional","affiliation":[{"name":"Jinhua Institute of Zhejiang University","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, \rZhejiang University, Hangzhou 310058, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, \rZhejiang University, Hangzhou 310058, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, \rZhejiang University, Hangzhou 310058, PR China."},{"name":"Jinhua Institute of Zhejiang University","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuesong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, \rZhejiang University, Hangzhou 310058, PR China."},{"name":"Jinhua Institute of Zhejiang University","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9763-383X","authenticated-orcid":true,"given":"Lihua","family":"Peng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, \rZhejiang University, Hangzhou 310058, PR China."},{"name":"Jinhua Institute of Zhejiang University","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00218-X"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi8287"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01478-2"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101263"},{"issue":"1","key":"e_1_3_4_6_2","first-page":"105","article-title":"Neuroprotective effects of kukoamine A on 6-OHDA-induced Parkinson\u2019s model through apoptosis and iron accumulation inhibition","volume":"13","author":"Li X","year":"2021","unstructured":"Li X, Jiang X, Chu H, Zhao Q, Ding H, Cai C. 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