{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:27:09Z","timestamp":1787243229357,"version":"build-2736575974"},"reference-count":79,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601121"],"award-info":[{"award-number":["81601121"]}],"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":["82401671"],"award-info":[{"award-number":["82401671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211235"],"award-info":[{"award-number":["BK20211235"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231050"],"award-info":[{"award-number":["BK20231050"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M651491"],"award-info":[{"award-number":["2020M651491"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012493","name":"Jiangsu Province Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020Z037"],"award-info":[{"award-number":["2020Z037"]}],"id":[{"id":"10.13039\/100012493","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010014","name":"Six Talent Peaks Project in Jiangsu Province","doi-asserted-by":"publisher","award":["SZCY\u2010003"],"award-info":[{"award-number":["SZCY\u2010003"]}],"id":[{"id":"10.13039\/501100010014","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["JUSRP123070"],"award-info":[{"award-number":["JUSRP123070"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Deficits in the autophagy\u2010lysosomal pathway facilitate intracellular microtubule associated protein tau (MAPT) accumulation in Alzheimer disease (AD). Aerobic exercise (AE) has been recommended as a way to delay and treat AD, but the exact effects and mechanisms have not been fully elucidated. Here, we found that AE (8\u2010week treadmill running, 40\u2009min\/day, 5\u2009days\/week) alleviated autophagy\u2010lysosomal defects and MAPT pathology through the activation of \u03b22\u2010adrenergic receptors (\u03b22\u2010AR) in MAPT P301L mice. Molecular mechanistic investigations revealed that endosomal sorting complex required for transport (ESCRT) III subunit charged multivesicular body protein 4B (CHMP4B), which is essential for autophagosome\u2010lysosome fusion, was significantly decreased in the cerebral cortex of AD patients and the hippocampus of MAPT P301L mice. AE restored the levels of CHMP4B, which reversed autophagy\u2010lysosomal defects and reduced MAPT aggregation. Inhibition of \u03b22\u2010AR by propranolol (30\u2009mg\/kg, intragastric administration 1\u2009h before each AE session) restrained AE\u2010attenuated MAPT accumulation by inhibiting autophagy\u2010lysosomal flux in MAPT P301L mice. Our findings suggest that AE can alleviate autophagosome\u2010lysosome fusion deficits by promoting the \u03b22\u2010AR\u2010RXR\u03b1\u2010CHMP4B\u2010ESCRT\u2013III pathway, reducing pathological MAPT aggregation, which also reveals a novel theoretical basis for AE attenuating AD progression.<\/jats:p>","DOI":"10.1111\/acel.70184","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T07:34:45Z","timestamp":1753515285000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Aerobic Exercise Attenuates Autophagy\u2010Lysosomal Flux Deficits via \u03b22\u2010AR\u2010Mediated ESCRT\u2010III Subunit CHMP4B in Mice With Human MAPT P301L"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9113-151X","authenticated-orcid":false,"given":"Shu\u2010Guang","family":"Bi","sequence":"first","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-998X","authenticated-orcid":false,"given":"Haitao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Long","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"},{"name":"Department of Electrophysiology, Wuhan Children's Hospital (Wuhan Maternal and Children's Healthcare Center), Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ming","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang\u2010Zhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Chong","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Ting","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Juan","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1943-3717","authenticated-orcid":false,"given":"Gao\u2010Shang","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Fundamental Medicine, MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine Jiangnan University  Wuxi Jiangsu China"},{"name":"Department of Pathology Affiliated Hospital of Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102202"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00219-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.02.012"},{"issue":"6","key":"e_1_2_12_5_1","first-page":"402","article-title":"Physical Exercise, Cognition, and Brain Health in Aging","volume":"47","author":"Boa Sorte Silva N. C.","year":"2024","journal-title":"Trends in Neurosciences"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0800-08.2008"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.109"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/M17-1528"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2281-05.2005"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161163"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04183-x"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.20398"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12946"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.05.008"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312889"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S169565"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1633862"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.04.005"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006531200"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2420"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07206"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00146-2020"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2298"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.11.001"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.5.14811"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2019.04.003"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247136"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00434-2"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2168"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1577-6"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.07.029"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5384"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01084-8"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13526"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.040"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7033-9_17"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.195"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.118"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12831"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102202"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1197623"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801567105"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3559"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06639"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.10.84"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102356"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3232"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.2.113"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-54"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.605317"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2022.0609"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-020-04447-w"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0292-9"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.359"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2012.44.2.029"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2235196"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899753"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0966-09.2009"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.09.032"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh012"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113694"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.121"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1609"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12902"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-181175"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030604"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1567OC"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0177-4"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14408"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01812-5"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2281134"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202007061"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202217061"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5072"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32764-5"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1639301"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq7105"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:06:31Z","timestamp":1759961191000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,26]]},"references-count":79,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/acel.70184"],"URL":"https:\/\/doi.org\/10.1111\/acel.70184","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,26]]},"assertion":[{"value":"2025-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70184"}}