{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:59:28Z","timestamp":1788357568880,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007620","name":"Department of Education of Liaoning Province","doi-asserted-by":"publisher","award":["LJKQZ2021101"],"award-info":[{"award-number":["LJKQZ2021101"]}],"id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007620","name":"Department of Education of Liaoning Province","doi-asserted-by":"publisher","award":["LJ222510161002"],"award-info":[{"award-number":["LJ222510161002"]}],"id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101275"],"award-info":[{"award-number":["82101275"]}],"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":["82471464"],"award-info":[{"award-number":["82471464"]}],"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":["82101661"],"award-info":[{"award-number":["82101661"]}],"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":["U1908208"],"award-info":[{"award-number":["U1908208"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The abnormal accumulation of amyloid\u2010\u03b2 (A\u03b2) in the brain is a characteristic pathological change observed in patients with Alzheimer's disease (AD). Microglial phagocytosis, dependent on recycling through the retromer complex and cell membrane\u2010bound receptors, plays a vital role in clearing A\u03b2 from the brain. Previous studies have demonstrated the neurotrophic and neuroprotective effects of Scorpion Venom Heat\u2010Resistant Synthetic Peptide (SVHRSP); however, its impacts on cognitive function remain unclear. The present study aims to investigate the impact of SVHRSP on cognitive function in APP\/PS1 transgenic mice and underlying mechanisms associated with microglial retromer complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>SVHRSP and 3\u2010methyladenine (3\u2010MA) were intraperitoneally injected at 7.5\u00a0months to investigate their effects on cognitive dysfunction in APP\/PS1 mice. Following behavioural testing, brain samples were harvested 24\u2009h later for electrophysiological recordings, analysis of protein and gene expression, and histological assessment. The role of microglial retromer complex was examined using primary microglia cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>SVHRSP treatment effectively improved AD\u2010related pathological features, including cognitive impairment, neuronal loss, impaired synaptic plasticity, neuroinflammation, and A\u03b2 deposition in APP\/PS1 mice. Both in vivo and in vitro studies revealed that SVHRSP treatment increased expression of retromer complex protein VPS35. 3\u2010MA, a specific class III phosphoinositide 3\u2010kinase (PI3K) inhibitor that prevents autophagosome formation, reduced retromer complex protein expression and hindered the cognitive function improvements of SVHRSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our findings suggest that SVHRSP may enhance microglial phagocytosis by modulating retromer complex activity, thereby alleviating A\u03b2 accumulation and improving cognitive dysfunction in AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70124","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T05:05:47Z","timestamp":1752555947000},"page":"5391-5408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Scorpion venom heat\u2010resistant synthetic peptide improves cognitive dysfunction of APP\/PS1 mice through microglial retromer complex"],"prefix":"10.1111","volume":"182","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"},{"name":"Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Xia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"},{"name":"National\u2010Local Joint Engineering Research Center for Drug\u2010Research and Development (R&amp;D) of Neurodegenerative Diseases Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Gang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"},{"name":"School of Special Education and Rehabilitation Binzhou Medical University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song\u2010Yu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u2010Na","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010Lin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Fa","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao\u2010Ran","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao\u2010Hang","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Special Education and Rehabilitation Binzhou Medical University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Piao","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"National\u2010Local Joint Engineering Research Center for Drug\u2010Research and Development (R&amp;D) of Neurodegenerative Diseases Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-8636","authenticated-orcid":false,"given":"Shao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3621-17.2018"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.03.009"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00090"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.856376"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205015666180702105740"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.02.010"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.128539"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2019-0058"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006304"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-48"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.16-14-04491.1996"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0041-0101(02)00142-3"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2022.09.022"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.10.011"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201709069"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.040"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15054"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10646-021-02439-w"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.10.121"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2005.04.008"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0433-4"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15502"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.06.046"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad-201178"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.12.017"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3250"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(83)90048-9"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802545105"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad-2010-1221"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2303"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa064"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1202-06.2006"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113613"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2741"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26040953"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2019.1026"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110262"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02422-0"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10274"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01343-y"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02565-0"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20667"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3896"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176704"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01273-8"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.02.001"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S200490"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101622"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929866525666180614114307"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0221-3"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1385\/jmn:23:1-2:105"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.Mr0818-319r"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13060628"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.919269"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201105109"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105768"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218144"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.704715"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.68.228"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13593"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00079"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.26164"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9366-0"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.06.241"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116497"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306241"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T07:45:20Z","timestamp":1759823120000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":74,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/bph.70124"],"URL":"https:\/\/doi.org\/10.1111\/bph.70124","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]},"assertion":[{"value":"2024-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}