{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:52:44Z","timestamp":1772985164398,"version":"3.50.1"},"reference-count":78,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["STI2030\u2010MajorProjects2021ZD0201705"],"award-info":[{"award-number":["STI2030\u2010MajorProjects2021ZD0201705"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82371576"],"award-info":[{"award-number":["NSFC82371576"]}],"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":["BZZ19J005"],"award-info":[{"award-number":["BZZ19J005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease characterized by progressive loss of motor neurons. Current clinically available drugs targeting neurons show minor survival extension and no motor improvement in ALS patients. This shifts the focus of ALS research toward non\u2010neuronal cells, particularly microglia, a critical driver of ALS pathogenesis. Highly druggable ion channels are key regulators of microglia function. Here, Hydrogen voltage gated channel 1 (HVCN1) was screened out as the most highly expressed ion channel in microglia, and was upregulated in microglia of\n                    <jats:italic>\n                      SOD1\n                      <jats:sup>G93A<\/jats:sup>\n                    <\/jats:italic>\n                    mice and patients. Deletion of HVCN1 in microglia increased motor neuron survival, rescued the innervated neuromuscular junctions in the muscle, reduced glial activation and decreased the level of both misfolded protein and myelin debris in the ALS mice. Importantly, these pathological improvements were translated into significant motor improvement and survival extension in the ALS mice, exhibiting better effects than the current clinical drugs. HVCN1 deletion enhanced microglia migration and their homeostatic state with elevated neurotrophic functions. Mechanistically, HVCN1 ablation promoted microglial migration via suppressing Akt signaling. Our results identify HVCN1 as a novel promising therapeutic target for ALS, opening a new avenue to further develop specific inhibitors for HVCN1 to alleviates ALS.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512149","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:34:57Z","timestamp":1767587697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microglial HVCN1 Deficiency Improves Movement and Survival of\n                    <i>\n                      SOD1\n                      <sup>G93A<\/sup>\n                    <\/i>\n                    ALS Mice by Enhancing Microglial Migration and Neuroprotection"],"prefix":"10.1002","volume":"13","author":[{"given":"Fan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke\u2010Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lang\u2010Jian","family":"Zhu","sequence":"additional","affiliation":[{"name":"BGI Research  Hangzhou China"},{"name":"BGI Research  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Jue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Ru","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu\u2010Hua","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Kang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"},{"name":"Basic Medical Experimental Teaching Center Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao\u2010Jun","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di\u2010Xian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Key Discipline of Human Anatomy Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao\u2010Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Discipline of Human Anatomy Southern Medical University  Guangzhou China"},{"name":"Department of Gastroenterology Jinling Hospital Medical School of Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"BGI Research  Hangzhou China"},{"name":"BGI Research  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010Nong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1135-9743","authenticated-orcid":false,"given":"Jing\u2010Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology System Medicine Research Center NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Hangzhou Zhejiang China"},{"name":"Center of Cryo\u2010Electron Microscopy Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000911"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01272-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010023\u201000891\u20102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00592-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-075037"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001447.pub3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.4893"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010024\u201012437\u20107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010025\u201007994\u20102"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001588\u20100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.053"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25251"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039216"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.12.012"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0242-x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104925"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.12.007"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10061239"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010022\u201004461\u20105"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.07.002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt259"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000612\u20102"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860\u201014.2014"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3059"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.768059"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010023\u201001053\u20106"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14925"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010022\u201000616\u2010y"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030582"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI139741"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04424-7"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04436-3"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.75"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.1045647"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.108872"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2021.04.008"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24304"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.008"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.07.003"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049596\u20100"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.032"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjt028"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000495"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.064"},{"key":"e_1_2_9_47_1","first-page":"1","volume-title":"GeneReviews\u00ae [Internet]","author":"Siddique N."},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010023\u201001070\u20106"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2120750119"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.013"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2024.101312"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.07.001"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1632346"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1054006"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.06.018"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083854"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2024.11.053"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147814"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227522"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1843"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.06.197"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091837"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640\u2010019\u20100003\u2010y"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601515"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.001"},{"issue":"10","key":"e_1_2_9_67_1","first-page":"2162","article-title":"Protein Kinase Inhibitors for Amyotrophic Lateral Sclerosis Therapy (vol 178, pg 1316, 2021)","volume":"178","author":"Palomo V.","year":"2021","journal-title":"British Journal of Pharmacology"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.014"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.816439"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201007548\u20105"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.01.026"},{"issue":"3","key":"e_1_2_9_72_1","first-page":"675","article-title":"Amelioration of Amyotrophic Lateral Sclerosis in SOD1G93A Mice by M2Microglia From Transplanted Marrow","volume":"33","author":"Epperly M. W.","year":"2019","journal-title":"In Vivo (Athens, Greece)"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2022.02.001"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62636"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.3791\/2610\u2010v"},{"key":"e_1_2_9_76_1","article-title":"The Neuromuscular Junction: Measuring Synapse Size, Fragmentation and Changes in Synaptic Protein Density Using Confocal Fluorescence Microscopy","volume":"94","author":"Tse N.","year":"2014","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1082180"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.70"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3125"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202512149","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202512149","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202512149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:00:21Z","timestamp":1772964021000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202512149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,4]]},"references-count":78,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/advs.202512149"],"URL":"https:\/\/doi.org\/10.1002\/advs.202512149","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,4]]},"assertion":[{"value":"2025-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12149"}}