{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:42:45Z","timestamp":1792179765989,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["I01 BX004626"],"award-info":[{"award-number":["I01 BX004626"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS073899"],"award-info":[{"award-number":["R01 NS073899"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG\u201022\u2010974562"],"award-info":[{"award-number":["AARG\u201022\u2010974562"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>FKBP51, also known as FK506\u2010binding protein 51, is a molecular chaperone and scaffolding protein with significant roles in regulating hormone signaling and responding to stress. Genetic variants in <jats:italic>FKBP5<\/jats:italic>, which encodes FKBP51, have been implicated in a growing number of neuropsychiatric disorders, which has spurred efforts to target FKBP51 therapeutically. However, the molecular mechanisms and sub\u2010anatomical regions influenced by FKBP51 in these disorders are not fully understood. In this study, we aimed to examine the impact of <jats:italic>Fkbp5<\/jats:italic> ablation using circadian phenotyping and molecular analyses. Our findings revealed that the lack of FKBP51 did not significantly alter circadian rhythms, as detected by wheel\u2010running activity, but did offer protection against stress\u2010mediated disruptions in rhythmicity in a sex\u2010dependent manner. Protein changes in <jats:italic>Fkbp5<\/jats:italic> KO mice, as measured by histology and proteomics, revealed alterations in a brain region\u2010 and sex\u2010dependent manner. Notably, regardless of sex, aged <jats:italic>Fkbp5<\/jats:italic> KOs showed elevated MYCBP2, FBXO45, and SPRYD3 levels, which are associated with neuronal\u2010cell adhesion and synaptic integrity. Additionally, pathways such as serotonin receptor signaling and S100 family signaling were differentially regulated in <jats:italic>Fkbp5<\/jats:italic> KO mice. Weighted protein correlation network analysis identified protein networks linked with synaptic transmission and neuroinflammation. The information generated by this work can be used to better understand the molecular changes in the brain during aging and in the absence of <jats:italic>Fkbp5<\/jats:italic>, which has implications for the continued development of FKBP51\u2010focused therapeutics for stress\u2010related disorders.<\/jats:p>","DOI":"10.1111\/acel.14314","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T09:54:46Z","timestamp":1725357286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>Fkbp5<\/i> gene deletion: Circadian rhythm profile and brain proteomics in aged mice"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-1920","authenticated-orcid":false,"given":"Niat T.","family":"Gebru","sequence":"first","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Guergues","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Verdina","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Wohlfahrt","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra S.","family":"Armendariz","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsilla","family":"Gray","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Beaulieu\u2010Abdelahad","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Stanley M.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Gulick","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-5564","authenticated-orcid":false,"given":"Laura J.","family":"Blair","sequence":"additional","affiliation":[{"name":"Byrd Alzheimer's Center and Research Institute  Tampa Florida USA"},{"name":"Department of Molecular Medicine University of South Florida  Tampa Florida USA"},{"name":"Research and Development James A. Haley Veterans Hospital  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac364"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12112"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001079"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111166"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09938"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0242\u201018.2019"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.89176"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006356"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.015362"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.582882"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00338\u201009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122614"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13064\u2010016\u20100063\u20100"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2020.103753"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901777R"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095796"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22358"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847699"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.113.006445"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2834"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010019\u20100521\u20109"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u20109\u2010559"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/77046"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2011.03.006"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1537\u201011.2011"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00539\u201019"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217105"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024840"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1038"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwz002"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.11.011"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107241"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00364\u201009"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14153029"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016883"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015\u20101996"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1117571"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062194"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.07.023"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2300722120"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010020\u20100694\u20100"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2011.03.008"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.035451.114"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.07.067"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1486"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.14314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T04:43:23Z","timestamp":1733978603000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.14314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,3]]},"references-count":45,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/acel.14314"],"URL":"https:\/\/doi.org\/10.1111\/acel.14314","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,3]]},"assertion":[{"value":"2024-02-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14314"}}