{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T06:26:40Z","timestamp":1777184800520,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Parkinson's disease (PD) is a neurodegenerative disorder that gets exacerbated by vascular injury. Neural stem cell\u2010derived exosomes (NSC\u2010Exos) display effective neuroprotective properties in PD models. Cell division control protein 42 (CDC42) is connected to angiogenesis, but its effects in PD remain undefined. This research aims to reveal the role of CDC42 in PD. First, we applied 1\u2010methyl\u20104\u2010phenylpyridinium (MPP<jats:sup>+<\/jats:sup>) to induce the human cerebral microvascular endothelial cells (HCMECs) model and evaluated cell viability and ferroptosis. Then, we characterized NSC\u2010Exos. Next, to appraise the effect of hypoxia\u2010pretreated NSC\u2010Exos (H\u2010NSC\u2010Exos) on the MPP<jats:sup>+<\/jats:sup>\u2010induced cells model, we examined angiogenesis and ferroptosis in HCMECs. Moreover, we constructed the PD mice model using 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) and tested the behavioral experiments and vascular injury of mice. Furthermore, we examined cellular ferroptosis and angiogenesis after knockdown of CDC42. Additionally, we investigated the interaction of CDC42 with Acyl\u2010CoA synthetase long\u2010chain family member 4 (ACSL4) and detected cellular ferroptosis and angiogenesis after overexpression of ACSL4. We found that H\u2010NSC\u2010Exos reversed the MPP<jats:sup>+<\/jats:sup>\u2010induced decrease in HCMECs viability and migration, lowered lipid\u2010reactive oxygen species (lipid\u2010ROS) levels, suppressed ferroptosis, and facilitated angiogenesis. Moreover, H\u2010NSC\u2010Exos attenuated MPTP\u2010induced PD development, vascular injury, and ferroptosis in mice. H\u2010NSC\u2010Exos with the knockdown of CDC42 reduced cell viability and angiogenesis and raised ferroptosis and lipid\u2010ROS levels, which were reversed by ferrostatin\u20101 and liproxstatin\u20101. CDC42 interacted with ACSL4. Furthermore, overexpression of ACSL4 aggravated the above effects of H\u2010NSC\u2010Exos in which CDC42 was knocked down. Our study reveals that H\u2010NSC\u2010Exos\u2010derived CDC42 inhibited ACSL4\u2010related ferroptosis to alleviate vascular injury in PD mice models. CDC42 may serve as a potent therapeutic target for PD treatment.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70027-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.70027","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:11:40Z","timestamp":1741727500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exosome\u2010Derived <scp>CDC42<\/scp> From Hypoxia\u2010Pretreated Neural Stem Cells Inhibits <scp>ACSL4<\/scp>\u2010Related Ferroptosis to Alleviate Vascular Injury in Parkinson's Disease Mice Models"],"prefix":"10.1111","volume":"169","author":[{"given":"You","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junwen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiameng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-2284","authenticated-orcid":false,"given":"Zhengtao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College Central South University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106374"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00480-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02320-1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103211"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1705-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-020-02961-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.09.025"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.30802\/AALAS-JAALAS-21-000125"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00900-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2239"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.54755"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-020-02167-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01293-6"},{"key":"e_1_2_10_15_1","first-page":"257","article-title":"Double Immunofluorescence Labeling for CD31 and CD105 as a Marker for Polyether Polyurethane\u2010Induced Angiogenesis in Mice","volume":"34","author":"Figueiredo C. C.","year":"2019","journal-title":"Histology and Histopathology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-023-01388-8"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14823"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb45030127"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7098463"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.355820"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04638-x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51480"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.914027"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21939"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01356-2"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002766R"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1726-7"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.09.026"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2020.101890"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2019.03.001"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-023-00269-3"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-018-1903-3"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0297-y"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v15.i7.687"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.05.003"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108528"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010449"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15112"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-023-01382-4"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00030-2"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.02.003"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-315985"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2020.1221"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13588"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.05.002"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03262-9"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00818-3"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.49"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30195"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c22671"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.368300"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2022.5199"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T17:53:52Z","timestamp":1744566832000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/jnc.70027"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70027","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70027"}}