{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:23:08Z","timestamp":1762917788509,"version":"build-2065373602"},"reference-count":38,"publisher":"Wiley","issue":"13-14","license":[{"start":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T00:00:00Z","timestamp":1498435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH Ruth L. Kirschstein National Research Service","award":["T32 HL\/NS 07913"],"award-info":[{"award-number":["T32 HL\/NS 07913"]}]},{"name":"Sleep Medicine Neurobiology and Epidemiology"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>Narcolepsy is a disabling neurological disorder of sleepiness linked to the loss of neurons producing orexin neuropeptides in the hypothalamus. Two well\u2010characterized phenotypic mouse models of narcolepsy, loss\u2010of\u2010function (orexin\u2010knockout), and progressive loss of orexin (orexin\/ataxin\u20103) exist. The open question is whether the proteomics signatures of the hypothalamus would be different between the two models. To address this gap, we utilized a label\u2010free proteomics approach and conducted a hypothalamic proteome analysis by comparing each disease model to that of wild type. Following data processing and statistical analysis, 14\u00a0484 peptides mapping to 2282 nonredundant proteins were identified, of which 39 proteins showed significant differences in protein expression across groups. Altered proteins in both models showed commonalties in pathways for mitochondrial dysfunction and neuronal degeneration, as well as altered proteins related to inflammatory demyelination, insulin resistance, metabolic responses, and the dopaminergic and monoaminergic systems. Model\u2010specific alterations in insulin degraded enzyme (IDE) and synaptosomal\u2010associated protein\u201025 were unique to orexin\u2010KO and orexin\/ataxin\u20103, respectively. For both models, proteomics not only identified clinically suspected consequences of orexin loss on energy homeostasis and neurotransmitter systems, but also identified commonalities in inflammation and degeneration despite the entirely different genetic basis of the two mouse models.<\/jats:p>","DOI":"10.1002\/pmic.201600478","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T20:04:51Z","timestamp":1495569891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic profiling of the hypothalamus in two mouse models of narcolepsy"],"prefix":"10.1002","volume":"17","author":[{"given":"Sausan","family":"Azzam","sequence":"first","affiliation":[{"name":"Center for Proteomics and Bioinformatics Department of Nutrition Case Western Reserve University  Cleveland OH USA"},{"name":"Pulmonary Critical Care and Sleep Medicine Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Schlatzer","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Bioinformatics Department of Nutrition Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Nethery","sequence":"additional","affiliation":[{"name":"Pulmonary Critical Care and Sleep Medicine Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dania","family":"Saleh","sequence":"additional","affiliation":[{"name":"Kent State University  Kent OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolin","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Bioinformatics Department of Nutrition Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afaf","family":"Akladious","sequence":"additional","affiliation":[{"name":"Medical Service Louis Stokes Cleveland DVA Medical Center  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Chance","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Bioinformatics Department of Nutrition Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kingman P.","family":"Strohl","sequence":"additional","affiliation":[{"name":"Pulmonary Critical Care and Sleep Medicine Case Western Reserve University  Cleveland OH USA"},{"name":"Medical Service Louis Stokes Cleveland DVA Medical Center  Cleveland OH USA"},{"name":"Department of Medicine University Hospitals Case Medical Center  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2013.00028"},{"key":"e_1_2_9_3_1","first-page":"81","article-title":"The hypocretin\/orexin system in sleep disorders: preclinical insights and clinical progress","volume":"8","author":"Chow M.","year":"2016","journal-title":"Nat. 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