{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:47Z","timestamp":1790618267229,"version":"4.1.0"},"reference-count":83,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["823B2027"],"award-info":[{"award-number":["823B2027"]}],"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>White matter (WM) abnormalities contribute to cognitive decline in Alzheimer's disease (AD). However, the mechanisms underlying AD\u2010associated WM vulnerability remain incompletely understood, and effective therapeutic strategies to improve WM pathology are still limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      \u2010specific RNAscope combined with Olig2 immunostaining was used to assess the cellular distribution of\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      transcripts. Oligodendrocyte\u2010targeted adeno\u2010associated virus (AAV)\u2010mediated\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      knockdown was performed in 5\u2009\u00d7\u2009FAD mice.\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      overexpression was conducted in primary oligodendrocyte precursor cells (OPCs) in\u00a0vitro. Phosphoproteomic profiling, co\u2010immunoprecipitation, Phos\u2010tag Western blot, and phospho\u2010site mutagenesis were used to identify downstream mechanisms. A bilateral common carotid artery stenosis (BCAS) model was employed to assess broader relevance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      mRNA was predominantly elevated in oligodendrocyte\u2010lineage cells of 5\u2009\u00d7\u2009FAD mice prior to overt myelin loss. Targeted knockdown of oligodendroglial\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      ameliorated cognitive deficits, preserved myelin ultrastructure, and promoted oligodendrocyte maturation. Conversely,\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      overexpression arrested OPC differentiation and suppressed myelin gene expression in\u00a0vitro. Mechanistically, SGK1.1 promoted HDAC2 phosphorylation at S422\/S424, and blocking this phosphorylation partially reversed SGK1.1\u2010induced maturation deficits. Furthermore, oligodendrocyte\u2010targeted\n                      <jats:italic>Sgk1.1<\/jats:italic>\n                      overexpression exacerbated WM injury and cognitive impairment in the BCAS model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identify oligodendrocyte\u2010targeted SGK1.1 inhibition as a tractable therapeutic strategy to preserve WM integrity and cognitive function, and define HDAC2 S422\/S424 phosphorylation as a mechanistic node linking SGK1.1 signaling to impaired myelination in AD and related demyelinating disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71150","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:17:35Z","timestamp":1788931055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oligodendrocyte\u2010Targeted\n                    <scp>SGK1.1<\/scp>\n                    Inhibition Alleviates White Matter Injury and Cognitive Impairment in Alzheimer's Disease via Modulation of\u00a0\n                    <scp>HDAC2<\/scp>\n                    Phosphorylation"],"prefix":"10.1002","volume":"32","author":[{"given":"Shiji","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"},{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3310-0844","authenticated-orcid":false,"given":"Chao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1875-9599","authenticated-orcid":false,"given":"Zhen","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanjing Drum Tower Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-0140","authenticated-orcid":false,"given":"Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"},{"name":"MOE Key Laboratory of Model Animal for Disease Study Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5496-3673","authenticated-orcid":false,"given":"Yuhao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashuo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8230-349X","authenticated-orcid":false,"given":"Xinyu","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2963-0888","authenticated-orcid":false,"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5288-0319","authenticated-orcid":false,"given":"Yun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"},{"name":"Department of Neurology, Nanjing Drum Tower Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing University  Nanjing China"},{"name":"Jiangsu Key Laboratory for Molecular Medicine, Medical School Nanjing University  Nanjing China"},{"name":"Nanjing Neurology Clinical Medical Centre, and Centre for Central Nervous Disease and Neuroscience  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4696-9696","authenticated-orcid":false,"given":"Xiaolei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.2"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.01.009"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.056"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23654"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2025.1601"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.05.019"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0657-2"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06120-6"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0539-4"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1553-10.2010"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.10.013"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254960"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-013101"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09614"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.136"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041359"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.031"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11314"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42293-4"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0515-3"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01730-3"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.2.243"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200066"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/915041"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.08.004"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2010.01.007"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2333"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.5.2.11160"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03599-4"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105590200"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.11.3024"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.507210"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3442-12.2013"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.179206"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc8096"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-025-03225-4"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-022-03710-0"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56854-2"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019859"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175075"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800958105"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202202976"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01257-5"},{"issue":"3","key":"e_1_2_14_49_1","first-page":"599","article-title":"Gene Therapy Targeting Oligodendrocytes Provides Therapeutic Benefit in a Leukodystrophy Model","volume":"140","author":"Georgiou E.","year":"2017","journal-title":"Brain"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00425-w"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190927"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.03.008"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00803-8"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1379.021"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.07.009"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.04.030"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.05.012"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111189"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.4.2031"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00081.2005"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102036"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108821"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805055200"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab115"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.03.123"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100087R"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-176891"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001625"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.07.005"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1448-9"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.05.112"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201174200"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204149200"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.04.002"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01590-1"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.19943"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0334-7"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02780-3"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000143725.19053.60"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4325"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1484-9"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-021-01054-y"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4693"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3599"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.71150","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:13:13Z","timestamp":1790615593000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.71150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":83,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cns.71150"],"URL":"https:\/\/doi.org\/10.1002\/cns.71150","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71150"}}