{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:27:32Z","timestamp":1784590052363,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2025,11,27]]},"abstract":"<jats:p>\n                    Despite numerous therapeutic attempts of Alzheimer's disease (AD), treatment options remain limited. Targeting microglia (MG) polarization from M1 to M2 is considered a promising approach, yet no drug specifically modulating this transition has been identified. The spleen tyrosine kinase (Syk) has emerged as a potential therapeutic target due to its role in regulating AD risk genes and promoting Amyloid\u2010\u03b2 (A\u03b2) clearance. Herein, a microglial reporter gene screening model targeting\n                    <jats:italic>Syk<\/jats:italic>\n                    is developed and two small molecules, neochlorogenic acid (NCGA) and L\u2010arabinitol (L\u2010Ara), that can upregulate\n                    <jats:italic>Syk<\/jats:italic>\n                    gene expression, leading to the activation of MG M2 phenotype, are identified. Furthermore, these compounds markedly enhance the capacity of MG to migrate toward A\u03b2 and phagocytose A\u03b2. However, when\n                    <jats:italic>Syk<\/jats:italic>\n                    expression is silenced using shRNA, the ability of these small molecules to induce the MG M2 phenotype and promote A\u03b2 phagocytosis by MG is substantially attenuated. These findings offer new insights into AD therapy development.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202500515","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:45:40Z","timestamp":1761659140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Drug Screening Targeting Upregulation of Syk Gene Identifies Neochlorogenic Acid and L\u2010Arabinitol Capable of Inducing the M2 Phenotype of Microglia in Alzheimer's Disease"],"prefix":"10.1002","volume":"26","author":[{"given":"Difei","family":"Hu","sequence":"first","affiliation":[{"name":"Beijing Life Science Academy  Beijing 102209 China"},{"name":"New Cornerstone Science Laboratory Department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianling","family":"Li","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory Department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeyin","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy  Beijing 102209 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory Department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicong","family":"Dai","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy  Beijing 102209 China"},{"name":"New Cornerstone Science Laboratory Department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1514-0562","authenticated-orcid":false,"given":"Xucong","family":"Teng","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy  Beijing 102209 China"},{"name":"Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at Microscale University of Science and Technology of China  Hefei 230026 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9389-4928","authenticated-orcid":false,"given":"Hongwei","family":"Hou","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy  Beijing 102209 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-7352","authenticated-orcid":false,"given":"Jinghong","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy  Beijing 102209 China"},{"name":"New Cornerstone Science Laboratory Department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology Tsinghua University  Beijing 100084 China"},{"name":"Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at Microscale University of Science and Technology of China  Hefei 230026 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-00940-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004568"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.03.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4017"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.07.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-012-0181-2"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04536-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.2.547"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1407"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.03.004"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1239"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23968"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00457"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211851"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b05650"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.04.014"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.801"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1088-4"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.008"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.07.007"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.030"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.033"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2006.053"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2007.17"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900909"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1432609100"},{"key":"e_1_2_7_33_1","doi-asserted-by":"crossref","unstructured":"L.Qin X.Wu M. 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