{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:11:38Z","timestamp":1780913498816,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":["82301626"],"award-info":[{"award-number":["82301626"]}],"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Both cytosolic phospholipase A2 (PLA2G4A)\u2010induced lysosomal membrane disruption and glycogen synthase kinase\u20103\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (GSK3\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      )\u2010mediated lysosomal dysfunction have been implicated in neurodegeneration, with a potential regulatory relationship between these two pathways. We recently identified AS1842856 (AS) as a suppressor of GSK3\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      . This study was therefore designed to investigate whether AS mitigates Alzheimer's disease (AD) progression by targeting PLA2G4A to restore lysosomal homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The therapeutic potential of AS was investigated in APP\/PS1 mice by analyzing cognitive function,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010amyloid (A\n                      <jats:italic>\u03b2<\/jats:italic>\n                      ) load, and lysosomal integrity, with its mechanism of action further explored in N2a\u2010sw cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AS treatment reduced GSK3\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      expression in both APP\/PS1 mice and N2a\u2010sw cells. This suppression led to decreased PLA2G4A levels, restoration of lysosomal membrane integrity, and enhanced lysosomal degradation of A\n                      <jats:italic>\u03b2<\/jats:italic>\n                      . Consequently, AS administration alleviated A\n                      <jats:italic>\u03b2<\/jats:italic>\n                      burden and improved cognitive function in APP\/PS1 mice. Moreover, AS was found to inhibit NF\u2010\u03baB\u2010mediated PLA2G4A expression. Knockdown experiments further revealed that reduced GSK3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2014but not GSK3\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2014reproduced the suppressive effect on PLA2G4A.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study identified the GSK3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \/NF\u2010\u03baB\/PLA2G4A signaling axis as a novel therapeutic target in AD, and AS could inhibit this axis to mitigate A\n                      <jats:italic>\u03b2<\/jats:italic>\n                      pathology by promoting lysosomal degradation of A\n                      <jats:italic>\u03b2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70910","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:00:47Z","timestamp":1777388447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>AS1842856<\/scp>\n                    Reduces \u03b2\u2010Amyloid Burden via Inhibiting\n                    <scp>PLA2G4A<\/scp>\n                    \u2010Mediated Lysosomal Dysfunction in\n                    <scp>APP<\/scp>\n                    \/\n                    <scp>PS1<\/scp>\n                    Mice"],"prefix":"10.1002","volume":"32","author":[{"given":"Da\u2010Long","family":"He","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences Hainan Medical University  Haikou China"},{"name":"Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province Health Sciences Institute of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province Health Sciences Institute of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Jun","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province Health Sciences Institute of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Yao","family":"Wu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Min","family":"Qiu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2652-2085","authenticated-orcid":false,"given":"Yong\u2010Gang","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences Hainan Medical University  Haikou China"},{"name":"Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning Province Health Sciences Institute of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113208"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00878-1"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-025-01812-9"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.308070"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150379"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2309163"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1438"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1197623"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202102001"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01084-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.02.001"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107973"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.07.006"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103970"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.12.001"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2307136"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007627725251"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.07033.x"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R057588"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021353"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.065714"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024015560"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14336"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9314-z"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00542-2"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109597"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13531"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202300414"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02552-1"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118664"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17116"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8255"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0197-x"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026620666200106125910"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121119298"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.10.003"},{"issue":"2","key":"e_1_2_13_38_1","article-title":"Palladium Nanoparticles Degrade Advanced Glycation End Products via Valosin\u2010Containing Protein Mediated Autophagy to Attenuate High\u2010Glucose\/High\u2010Fat\u2010Induced Intervertebral Disc Degeneration","volume":"5","author":"Yang X.","year":"2025","journal-title":"Exploration (Beijing, China)"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2022.119243"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.05.148"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071679"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.286948"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201612148"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13010103"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/nep3.66"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2018.08.010"},{"issue":"6","key":"e_1_2_13_47_1","first-page":"2121","article-title":"Inherited Human cPLA(2alpha) Deficiency Is Associated With Impaired Eicosanoid Biosynthesis, Small Intestinal Ulceration, and Platelet Dysfunction","volume":"118","author":"Adler D. H.","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-010-8101-0"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2003.09.003"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05349.x"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1628538"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70910","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.70910","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:37:56Z","timestamp":1780911476000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.70910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cns.70910"],"URL":"https:\/\/doi.org\/10.1002\/cns.70910","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70910"}}