{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:31:11Z","timestamp":1786559471899,"version":"build-2736575974"},"reference-count":75,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"33","funder":[{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["XDB0730300"],"award-info":[{"award-number":["XDB0730300"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Niemann-Pick type C (NPC) disease is a lysosomal storage disorder primarily caused by mutations in the\n                    <jats:italic toggle=\"yes\">NPC1<\/jats:italic>\n                    gene. Most patients present with early-life symptoms including hepatosplenomegaly and digestive system impairment, followed by progressive neurodegeneration. However, effective therapeutic approaches to improve survival in NPC disease remain limited. In this study, using an\n                    <jats:italic toggle=\"yes\">npc1<\/jats:italic>\n                    -knockout (NPC1-KO) zebrafish model established in our laboratory, our team suggests that\n                    <jats:italic toggle=\"yes\">npc1<\/jats:italic>\n                    deficiency appears to correlate with marked down-regulation of superoxide dismutase 2 (Sod2) expression, concurrent with excessive oxidative stress (OS), mitochondrial dysfunction, and defective mitophagy. Treatment with Mito-TEMPO, a mitochondria-targeted antioxidant acting on SOD, increased survival rates and ameliorated cholesterol accumulation and liver function impairment in early-stage NPC1-KO zebrafish. The underlying mechanism may involve attenuation of OS and promotion of PINK1\/Parkin-dependent mitophagic flux through SOD2 enhancement. Our findings support Mito-TEMPO as a potential therapeutic agent and SOD2 as a possible target for NPC disease.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee0509","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:01:07Z","timestamp":1786557667000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Mito-TEMPO improves survival rates in\n                    <i>npc1<\/i>\n                    -knockout zebrafish by reducing oxidative stress and enhancing mitophagy via Sod2"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3520-7031","authenticated-orcid":true,"given":"Wenhao","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China."},{"name":"University of Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-8360","authenticated-orcid":true,"given":"Xudong","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China."},{"name":"Fisheries College, Hunan Agricultural University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6409-8799","authenticated-orcid":true,"given":"Ruyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China."},{"name":"University of Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3455-9615","authenticated-orcid":true,"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China."},{"name":"University of Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-333X","authenticated-orcid":true,"given":"Man","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China."},{"name":"University of Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3606-544X","authenticated-orcid":true,"given":"Hong","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China."},{"name":"University of Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145059"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207667"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-12"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70194-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014890108"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026613666131127160118"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-021-00842-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.770578"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082685"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.11.010"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081386"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw025"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.559914"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00493.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.09.008"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152925"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.045609"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118929"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00982"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.11.034"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.10.029"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adu5787"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.10.042"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070052"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds090"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.11.016"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology12101322"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/diseases6020043"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413356"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2004.08.010"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2018-0118"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116605"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2025.154221"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1474673"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2023.100988"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14222"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.08.021"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.377414"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01293-x"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.24-210"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00638-2"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.04.021"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.034165"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M012377"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10255"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1086\/302620"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030679"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-009-0175-3"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.90946"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0185-4"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13389"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20454-z"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2023.2213817"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.3390\/md19120655"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173374"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2021.100973"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07976"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011442117"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06770-y"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.636803"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2005.03.005"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27030811"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.11.045"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6394199"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e07310"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144068"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2019.121390"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2017.50.6.056"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.05.008"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.007"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.114052"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150587"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00162.2024"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.03.027"},{"key":"e_1_3_2_76_2","unstructured":"OECD OECD Guidelines for the Testing of Chemicals Test No. 236: Fish Embryo Acute Toxicity (FET) Test (Organisation for Economic Co-operation and Development Paris 2013)."}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aee0509","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:01:28Z","timestamp":1786557688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aee0509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":75,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2026,8,14]]}},"alternative-id":["10.1126\/sciadv.aee0509"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aee0509","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaee0509"}}