{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T17:01:07Z","timestamp":1762102867519,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of General Medical Sciences, United States","award":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"],"award-info":[{"award-number":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"]}]},{"name":"Office of the Director, National Institutes of Health, United States","award":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"],"award-info":[{"award-number":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"]}]},{"name":"National Institute on Drug Abuse, United States","award":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"],"award-info":[{"award-number":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"]}]},{"name":"National Library of Medicine, United States","award":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"],"award-info":[{"award-number":["R01 GM117208","R01 GM117208-03S1","S10 OD026882-01","S10 OD028614-01","P30DA054557","R01 LM12980"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with non-specific chemical oxidation from reactive oxygen species (ROS), whose chemistries are linked to various disease pathologies, including neurodegeneration. Emerging evidence shows MSox site occupancy is, in some cases, under enzymatic regulatory control, mediating cellular signaling, including phosphorylation and\/or calcium signaling, and raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL\/6 mouse has well-defined Alzheimer\u2019s and aging states. Using this model, we analyzed age-, sex-, and disease-dependent MSox speciation in the mouse hippocampus. In addition, we explored the chemical stability and statistical variance of oxidized peptide signals to understand the needed power for MSox-based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MSox with age as well as neuroinflammatory targets accumulating MSox with AD in proteome studies of the mouse hippocampus. Further, this paper establishes a foundation for reproducible and rigorous experimental MSox-omics appropriate for novel target identification in biological discovery and for biomarker analysis in ROS and other oxidation-linked diseases.<\/jats:p>","DOI":"10.3390\/ijms25126516","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T03:52:53Z","timestamp":1718337173000},"page":"6516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age- and Alzheimer\u2019s Disease-Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways"],"prefix":"10.3390","volume":"25","author":[{"given":"Filipa Blasco Tavares Pereira","family":"Lopes","sequence":"first","affiliation":[{"name":"Center for Proteomics and Bioinformatics, Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Schlatzer","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Bioinformatics, Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengzhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Computer and Data Sciences, Case School of Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serhan","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Computer and Data Sciences, Case School of Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Diseases, Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9578-3890","authenticated-orcid":false,"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"Center for Mitochondrial Diseases, Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5280-5738","authenticated-orcid":false,"given":"Marzieh","family":"Ayati","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Koyut\u00fcrk","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Bioinformatics, Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Department of Computer and Data Sciences, Case School of Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Chance","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Bioinformatics, Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/15216540051081056","article-title":"Oxidation of methionine in proteins: Roles in antioxidant defense and cellular regulation","volume":"50","author":"Levine","year":"2000","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbapap.2004.08.010","article-title":"Methionine oxidation and aging","volume":"1703","author":"Stadtman","year":"2005","journal-title":"Biochim. 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