{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:03:42Z","timestamp":1784127822519,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M703235"],"award-info":[{"award-number":["2021M703235"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515110669"],"award-info":[{"award-number":["2022A1515110669"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200355"],"award-info":[{"award-number":["82200355"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470243"],"award-info":[{"award-number":["82470243"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prion diseases are fatal neurodegenerative diseases caused by misfolded prion protein. DL\u20103\u2010n\u2010butylphthalide (NBP), a synthetic agent derived from celery seeds, exhibits neuroprotective effects in multiple neurological disorders. However, its effects against prion peptide\u2010induced neurotoxicity remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A PrP\n                      <jats:sup>106\u2010126<\/jats:sup>\n                      \u2010induced neurotoxicity model was established in N2a cells to evaluate the effects of NBP. Apoptosis, oxidative stress, mitochondrial function, mitochondrial dynamics, and respiratory chain integrity were assessed following NBP pretreatment. Mechanistic causality was examined using OPA1 knockdown, DRP1 overexpression, NRF2 inhibition, and NRF2 overexpression. Key findings were further validated in human iPSC\u2010derived neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NBP attenuated PrP\n                      <jats:sup>106\u2010126<\/jats:sup>\n                      \u2010induced neuronal apoptosis, decreasing cytochrome\n                      <jats:italic>c<\/jats:italic>\n                      release and caspase 3 cleavage. NBP also alleviated oxidative stress by lowering ROS and MDA levels, restoring T\u2010AOC and SOD activity, and increasing NRF2\/HO\u20101 signaling. In parallel, NBP preserved mitochondrial integrity and bioenergetics by maintaining MMP, ATP production, OCR, and mtDNA content, while sustaining respiratory chain complex expression and activity. NBP further normalized mitochondrial dynamics, restoring OPA1 levels and reducing DRP1 enrichment in mitochondrial fractions. Functionally, OPA1 knockdown, DRP1 overexpression, or NRF2 inhibition abolished NBP\u2010mediated protection, whereas NRF2 overexpression recapitulated key protective effects and normalized OPA1\/DRP1\u2010related markers. Consistent protective trends were observed in human iPSC\u2010derived neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      NBP mitigates PrP\n                      <jats:sup>106\u2010126<\/jats:sup>\n                      \u2010induced neurotoxicity by engaging NRF2\u2010dependent antioxidant signaling and preserving mitochondrial homeostasis, with associated normalization of OPA1\/DRP1\u2010related mitochondrial dynamics. These findings support further evaluation of NBP in prion disease\u2010relevant models.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70948","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:55:57Z","timestamp":1780412157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>DL<\/scp>\n                    \u20103\u2010n\u2010Butylphthalide Protects Against\n                    <scp>\n                      PrP\n                      <sup>106<\/sup>\n                    <\/scp>\n                    <sup>\u2212126<\/sup>\n                    \u2010Induced Neurotoxicity Through\n                    <scp>NRF2<\/scp>\n                    Signaling and\n                    <scp>OPA1<\/scp>\n                    \/\n                    <scp>DRP1<\/scp>\n                    \u2010Mediated Mitochondrial Dynamics"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7145-3820","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"first","affiliation":[{"name":"The Fifth Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong China"},{"name":"Department of Basic Research Guangzhou National Laboratory  Guangzhou Guangdong China"},{"name":"Center for Neurometabolism and Regenerative Medicine Bioland Laboratory  Guangzhou Guangdong China"},{"name":"The Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital  Qingyuan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Research Guangzhou National Laboratory  Guangzhou Guangdong China"},{"name":"Center for Neurometabolism and Regenerative Medicine Bioland Laboratory  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Basic Research Guangzhou National Laboratory  Guangzhou Guangdong China"},{"name":"Center for Neurometabolism and Regenerative Medicine Bioland Laboratory  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[{"name":"The Fifth Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong China"},{"name":"Department of Basic Research Guangzhou National Laboratory  Guangzhou Guangdong China"},{"name":"Center for Neurometabolism and Regenerative Medicine Bioland Laboratory  Guangzhou Guangdong China"},{"name":"The Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital  Qingyuan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2024.123119"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-013109"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2024.1324702"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102667"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05292"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.11.003"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1953-y"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12693"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.07.017"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X19500265"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527317666180612125843"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2024-003611"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1360932"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.10.024"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-00583-3"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.647266"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2024.110969"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.794770"},{"issue":"7","key":"e_1_2_12_20_1","first-page":"2109","article-title":"Dl\u20103\u2010n\u2010Butylphthalide Protects the Blood Brain Barrier of Cerebral Infarction by Activating the Nrf\u20102\/HO\u20101 Signaling Pathway in Mice","volume":"22","author":"Zhao Y. 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