{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T08:30:59Z","timestamp":1793694659616,"version":"4.5.1"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070954"],"award-info":[{"award-number":["32070954"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.phrs.2026.108478","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:43:00Z","timestamp":1789944180000},"page":"108478","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Compartment-specific inhibition of cytosolic Cathepsin B mitigates microglial senescence in the aging brain"],"prefix":"10.1016","volume":"233","author":[{"given":"Simeng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2732-3403","authenticated-orcid":false,"given":"Jian","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-8146","authenticated-orcid":false,"given":"Junjun","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2026.108478_bib1","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-023-05027-2","article-title":"Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype","volume":"6","author":"Matsudaira","year":"2023","journal-title":"Commun. Biol."},{"key":"10.1016\/j.phrs.2026.108478_bib2","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/s43587-021-00121-8","article-title":"Strategies for targeting senescent cells in human disease","volume":"1","author":"Gasek","year":"2021","journal-title":"Nat. Aging"},{"key":"10.1016\/j.phrs.2026.108478_bib3","first-page":"186","article-title":"Atlas of the aging mouse brain reveals white matter as vulnerable foci","author":"Hahn","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2026.108478_bib4","doi-asserted-by":"crossref","DOI":"10.1111\/acel.12832","article-title":"Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice","volume":"17","author":"Elmore","year":"2018","journal-title":"Aging Cell"},{"key":"10.1016\/j.phrs.2026.108478_bib5","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-11674-z","article-title":"Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model","volume":"10","author":"Spangenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phrs.2026.108478_bib6","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/s43587-023-00470-6","article-title":"Tubular lysosome induction couples animal starvation to healthy aging","volume":"3","author":"Villalobos","year":"2023","journal-title":"Nat. Aging"},{"key":"10.1016\/j.phrs.2026.108478_bib7","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.arr.2016.02.009","article-title":"Lysosomal cell death mechanisms in aging","volume":"32","author":"G\u00f3mez-Sintes","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.phrs.2026.108478_bib8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41419-023-05786-0","article-title":"Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways","volume":"14","author":"Xie","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.phrs.2026.108478_bib9","article-title":"Cathepsin B modulates microglial migration and phagocytosis of amyloid beta in Alzheimer's disease through PI3K-Akt signaling","author":"Jiang","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.phrs.2026.108478_bib10","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.bbi.2017.06.002","article-title":"Cathepsin B plays a critical role in inducing Alzheimer's disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice","volume":"65","author":"Wu","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.phrs.2026.108478_bib11","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.neuron.2008.10.001","article-title":"Cystatin C-cathepsin B axis regulates amyloid beta levels and associated neuronal deficits in an animal model of Alzheimer's disease","volume":"60","author":"Sun","year":"2008","journal-title":"Neuron"},{"key":"10.1016\/j.phrs.2026.108478_bib12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s11481-016-9721-6","article-title":"Cathepsin B improves ss-amyloidosis and learning and memory in models of Alzheimer's disease","volume":"12","author":"Embury","year":"2017","journal-title":"J. Neuroimmune Pharmacol."},{"key":"10.1016\/j.phrs.2026.108478_bib13","doi-asserted-by":"crossref","DOI":"10.1111\/acel.12856","article-title":"Increased expression and altered subcellular distribution of cathepsin B in microglia induce cognitive impairment through oxidative stress and inflammatory response in mice","volume":"18","author":"Ni","year":"2019","journal-title":"Aging Cell"},{"key":"10.1016\/j.phrs.2026.108478_bib14","doi-asserted-by":"crossref","first-page":"12488","DOI":"10.1523\/JNEUROSCI.1599-15.2015","article-title":"The critical role of proteolytic relay through cathepsins B and E in the phenotypic change of microglia\/macrophage","volume":"35","author":"Ni","year":"2015","journal-title":"J. Neurosci."},{"key":"10.1016\/j.phrs.2026.108478_bib15","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13707","article-title":"The lysosomal proteome of senescent cells contributes to the senescence secretome","volume":"21","author":"Rovira","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.phrs.2026.108478_bib16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0304-3940(89)90166-3","article-title":"Lysosome instability in aged rat-brain","volume":"97","author":"Nakamura","year":"1989","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.phrs.2026.108478_bib17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1006\/exnr.1994.1048","article-title":"Age-related-changes in activities and localizations of cathepsin-D, cathepsin-E, cathepsin-B, and cathepsin-L in the rat-brain tissues","volume":"126","author":"Nakanishi","year":"1994","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.phrs.2026.108478_bib18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4161\/epi.5.2.11080","article-title":"\u03b3H2AX as a molecular marker of aging and disease","volume":"5","author":"Mah","year":"2010","journal-title":"Epigenetics"},{"key":"10.1016\/j.phrs.2026.108478_bib19","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1515\/BC.2005.109","article-title":"Activation processing of cathepsin H impairs recognition by its propeptide","volume":"386","author":"Horn","year":"2005","journal-title":"Biol. Chem."},{"key":"10.1016\/j.phrs.2026.108478_bib20","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13338","article-title":"Cellular aging beyond cellular senescence: markers of senescence prior to cell cycle arrest in vitro and in vivo","volume":"20","author":"Ogrodnik","year":"2021","journal-title":"Aging Cell"},{"key":"10.1016\/j.phrs.2026.108478_bib21","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.1038\/s41467-022-32552-1","article-title":"A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues","volume":"13","author":"Saul","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phrs.2026.108478_bib22","first-page":"30","article-title":"Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease","volume":"1371","author":"Serrano-Puebla","year":"2016","journal-title":"Target. Lysosome"},{"key":"10.1016\/j.phrs.2026.108478_bib23","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/s43587-022-00290-0","article-title":"Alzheimer's disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment","volume":"2","author":"Chen","year":"2022","journal-title":"Nat. Aging"},{"key":"10.1016\/j.phrs.2026.108478_bib24","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1101\/gr.122226.111","article-title":"Analysis of alternative splicing associated with aging and neurodegeneration in the human brain","volume":"21","author":"Tollervey","year":"2011","journal-title":"Genome Res."},{"key":"10.1016\/j.phrs.2026.108478_bib25","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1021\/acschembio.1c00138","article-title":"Selective neutral pH inhibitor of cathepsin B designed based on cleavage preferences at cytosolic and lysosomal pH conditions","volume":"16","author":"Yoon","year":"2021","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.phrs.2026.108478_bib26","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1074\/jbc.M008944200","article-title":"Lysosomal protease pathways to apoptosis -: cleavage of Bid, not pro-caspases, is the most likely route","volume":"276","author":"Stoka","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phrs.2026.108478_bib27","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/ni.1631","article-title":"Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization","volume":"9","author":"Hornung","year":"2008","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.phrs.2026.108478_bib28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1126\/science.aaw9872","article-title":"Cysteine depletion induces pancreatic tumor ferroptosis in mice","volume":"368","author":"Badgley MA","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.phrs.2026.108478_bib29","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1084\/jem.20021952","article-title":"Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion","volume":"197","author":"Boya","year":"2003","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.phrs.2026.108478_bib30","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nm.2999","article-title":"Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth","volume":"19","author":"Bruchard","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.phrs.2026.108478_bib31","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1111\/acel.12646","article-title":"The emerging role of alternative splicing in senescence and aging","volume":"16","author":"Desch\u00eanes","year":"2017","journal-title":"Aging Cell"},{"key":"10.1016\/j.phrs.2026.108478_bib32","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-55607-x","article-title":"Splicing accuracy varies across human introns, tissues, age and disease","volume":"16","author":"Garc\u00eda-Ruiz","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phrs.2026.108478_bib33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/0003-9861(92)90290-D","article-title":"Ca074 methyl-ester \u2013 a proinhibitor for intracellular cathepsin-B","volume":"299","author":"Buttle","year":"1992","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.phrs.2026.108478_bib34","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1021\/acs.biochem.1c00684","article-title":"Molecular features of CA-074 pH-dependent inhibition of cathepsin B","volume":"61","author":"Yoon","year":"2022","journal-title":"Biochemistry"},{"key":"10.1016\/j.phrs.2026.108478_bib35","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2026.108478_bib36","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/brain\/awad361","article-title":"Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer's disease pathogenesis","volume":"147","author":"Yuyama","year":"2024","journal-title":"Brain"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826003932?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826003932?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T08:13:21Z","timestamp":1793693601000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661826003932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":36,"alternative-id":["S1043661826003932"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108478","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Compartment-specific inhibition of cytosolic Cathepsin B mitigates microglial senescence in the aging brain","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108478","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108478"}}