{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:41:31Z","timestamp":1776066091534,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260213"],"award-info":[{"award-number":["82260213"]}],"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":["82360202"],"award-info":[{"award-number":["82360202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inherited retinal degeneration (IRD) is a debilitating condition characterized by progressive loss of photoreceptor cells. However, the underlying mechanisms remain largely unclear. This study investigated the role of DNA topoisomerase II alpha (TOP2A) and its interplay with protein kinase G (PKG) and histone deacetylase (HDAC) in the\n                    <jats:italic>rd1<\/jats:italic>\n                    mouse model for IRD. Immunofluorescence and quantitative western blotting analyses were performed to evaluate the expression of TOP2A, PKG1, PKG2, HDAC1, and other related markers. TSC24 and suberoylanilide hydroxamic acid were used to specifically inhibit TOP2A and HDAC, respectively, in organotypic retinal explant cultures derived from wild\u2010type or\n                    <jats:italic>rd1<\/jats:italic>\n                    mice. Furthermore, we examined the effect of PKG activity on TOP2A phosphorylation using KT5823. Significant upregulation of TOP2A was observed in the\n                    <jats:italic>rd1<\/jats:italic>\n                    mouse retina compared with wild\u2010type controls, especially in the outer nuclear layer. Phosphorylation levels of TOP2A strongly correlated with photoreceptor cell death. Treatment with TSC24 significantly reduced TOP2A\u2010positive and TUNEL\u2010positive cells. TOP2A phosphorylation was accompanied by HDAC activation, which was mitigated by TSC24. PKG inhibition by KT5823 reduced TOP2A phosphorylation at specific residues and photoreceptor HDAC activity. Our findings position TOP2A in the PKG\u2010TOP2A\u2010HDAC photoreceptor degenerative pathway, offering new potential therapeutic targets for combating IRD\u2010type diseases.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70077-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70077","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T02:56:27Z","timestamp":1746413787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>PKG<\/scp>\n                    \u2010Mediated Phosphorylation of\n                    <scp>TOP2A<\/scp>\n                    Activates\n                    <scp>HDAC<\/scp>\n                    to Drive Photoreceptor Cell Death in\n                    <i>rd1<\/i>\n                    Mouse Inherited Retinal Degeneration"],"prefix":"10.1111","volume":"169","author":[{"given":"Yujie","family":"Dong","sequence":"first","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wandong","family":"Zuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"},{"name":"School of Clinical Medicine, Dali University  Dali Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunming","family":"Guo","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Cell Metabolism and Disease Center for Life Sciences, School of Life Sciences, Yunnan University  Kunming China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maorong","family":"Chen","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Cell Metabolism and Disease Center for Life Sciences, School of Life Sciences, Yunnan University  Kunming China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjiang","family":"Hou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhulin","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Paquet\u2010Durand","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, Eberhard\u2010Karls\u2010Universit\u00e4t T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-5993","authenticated-orcid":false,"given":"Kangwei","family":"Jiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yunnan Province Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.100975"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.12095"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166226"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002065"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123748"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04482-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2012069"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.15659"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13040581"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-022-00592-4"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867321666140601201337"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-022-01013-1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2023.108232"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S316145"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab079"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2021.01.001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000824200"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.41415"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759091415593066"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.840759"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241311200"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02439-0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166717"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1236826"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8872"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3102-20.2021"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.07.005"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119504"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25475"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0248-4900(88)90116-5"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031180"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00897-7"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2010.4"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00519723"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-39"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.12.012"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2015.07.005"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.11.007"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015277"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/81671"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add4920"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718792115"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S240577"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.64017"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-38117-6"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw626"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12030455"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0512"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.10.139"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.43140"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-27681-1_70"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24129836"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.938089"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70077","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.70077","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:44:19Z","timestamp":1776062659000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/jnc.70077"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70077","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNC.70077\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70077\/v1\/review1","asserted-by":"object"}]},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70077"}}