{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:07:53Z","timestamp":1789549673854,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01GM130091-02"],"award-info":[{"award-number":["1R01GM130091-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01GM130091-04"],"award-info":[{"award-number":["1R01GM130091-04"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["27773803"],"award-info":[{"award-number":["27773803"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["D-0005"],"award-info":[{"award-number":["D-0005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health Ricerca Corrente (RC)","doi-asserted-by":"publisher","award":["1R01GM130091-02"],"award-info":[{"award-number":["1R01GM130091-02"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health Ricerca Corrente (RC)","doi-asserted-by":"publisher","award":["1R01GM130091-04"],"award-info":[{"award-number":["1R01GM130091-04"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health Ricerca Corrente (RC)","doi-asserted-by":"publisher","award":["27773803"],"award-info":[{"award-number":["27773803"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health Ricerca Corrente (RC)","doi-asserted-by":"publisher","award":["D-0005"],"award-info":[{"award-number":["D-0005"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Robert A. Welch Foundation","doi-asserted-by":"publisher","award":["1R01GM130091-02"],"award-info":[{"award-number":["1R01GM130091-02"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Robert A. Welch Foundation","doi-asserted-by":"publisher","award":["1R01GM130091-04"],"award-info":[{"award-number":["1R01GM130091-04"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Robert A. Welch Foundation","doi-asserted-by":"publisher","award":["27773803"],"award-info":[{"award-number":["27773803"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Robert A. Welch Foundation","doi-asserted-by":"publisher","award":["D-0005"],"award-info":[{"award-number":["D-0005"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CH Foundation","award":["1R01GM130091-02"],"award-info":[{"award-number":["1R01GM130091-02"]}]},{"name":"CH Foundation","award":["1R01GM130091-04"],"award-info":[{"award-number":["1R01GM130091-04"]}]},{"name":"CH Foundation","award":["27773803"],"award-info":[{"award-number":["27773803"]}]},{"name":"CH Foundation","award":["D-0005"],"award-info":[{"award-number":["D-0005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Narcolepsy type 1 (NT1) is the most common type of narcolepsy known to be caused by the loss of specific neurons responsible for producing peptide neurotransmitters (orexins\/hypocretins), resulting in a sleep-wake cycle disorder. It is characterized by its association with cataplexy and abnormalities in rapid eye movement. To date, no cure has been established for this life-threatening condition. Misdiagnosis of NT1 is also quite common, although it is not exceedingly rare. Therefore, successfully identifying candidate serum biomarkers for NT1 would be a head start for accurate diagnosis and development of therapeutics for this disorder. This study aims to identify such potential serum biomarkers. A depletion protocol was employed for 27 human serum samples (16 NT1 and 11 healthy controls), followed by applying LC-MS\/MS bottom-up proteomics analysis, then LC-PRM-MS for validation. The comparison of the proteome profiles of the low-abundant proteins in the samples was then investigated based on age, sex, sample groups, and the presence of the Human Leukocyte Antigen (HLA) DQB1*0602 allele. The results were tracked to gene expression studies as well as system biology to identify key proteins and understand their relationship in the pathogenesis of NT1. Our results revealed 36 proteins significantly and differentially expressed. Among the impaired pathways and bioprocesses, the complement activation pathway is impaired by six of the differentially expressed proteins (DEPs). They are coded by the genes C2, CFB, C5, C1R, C1S, and MASP1, while 11 DEPs are involved in Acute Phase Response Signaling (APRS), which are coded by the genes FN1, AMBP, APOH, CFB, CP, ITIH2, C5, C2, F2, C1, and ITIH4. The combined AUCs of the downregulated and upregulated DEPs are 0.95 and 0.76, respectively. Overall, this study reveals potential serum-protein biomarkers of NT1 and explains the possible correlation between the biomarkers and pathophysiological effects, as well as important biochemical pathways involved in NT1.<\/jats:p>","DOI":"10.3390\/biom13030420","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T05:23:43Z","timestamp":1677129823000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["LC-MS\/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1250-7293","authenticated-orcid":false,"given":"Akeem","family":"Sanni","sequence":"first","affiliation":[{"name":"Chemistry and Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Goli","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-5615","authenticated-orcid":false,"given":"Junyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Barsa","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-6104","authenticated-orcid":false,"given":"Samer","family":"El Hayek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33124, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farid","family":"Talih","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartolo","family":"Lanuzza","sequence":"additional","affiliation":[{"name":"Sleep Research Centre, Department of Neurology IC, Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5008-6944","authenticated-orcid":false,"given":"Firas","family":"Kobeissy","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon"},{"name":"Multiomics & Biomarkers, Department of Neurobiology, Center for Neurotrauma, Morehouse School of Medicine (MSM), Atlanta, GA 30310, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Plazzi","sequence":"additional","affiliation":[{"name":"IRCCS, Instituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Moresco","sequence":"additional","affiliation":[{"name":"IRCCS, Instituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-3614","authenticated-orcid":false,"given":"Stefania","family":"Mondello","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6937-3065","authenticated-orcid":false,"given":"Raffaele","family":"Ferri","sequence":"additional","affiliation":[{"name":"Sleep Research Centre, Department of Neurology IC, Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6661-6073","authenticated-orcid":false,"given":"Yehia","family":"Mechref","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16100","DOI":"10.1038\/nrdp.2016.100","article-title":"Narcolepsy","volume":"3","author":"Kornum","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41582-019-0226-9","article-title":"Narcolepsy\u2014Clinical spectrum, aetiopathophysiology, diagnosis and treatment","volume":"15","author":"Bassetti","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1124\/pr.109.001321","article-title":"Orexin\/hypocretin: A neuropeptide at the interface of sleep, energy homeostasis, and reward system","volume":"61","author":"Tsujino","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.brainres.2019.04.013","article-title":"Untangling narcolepsy and diabetes: Pathomechanisms with eyes on therapeutic options","volume":"1718","author":"Mohammadi","year":"2019","journal-title":"Brain Res."},{"key":"ref_5","first-page":"320","article-title":"Criteria for the diagnosis of the narcoleptic syndrome","volume":"32","author":"Yoss","year":"1957","journal-title":"Proc. Staff Meet. Mayo Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1365-2869.2004.00422.x","article-title":"The clinical spectrum of narcolepsy with cataplexy: A reappraisal","volume":"13","author":"Sturzenegger","year":"2004","journal-title":"J. Sleep Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.5665\/sleep.4066","article-title":"HLA DQB1*06:02 negative narcolepsy with hypocretin\/orexin deficiency","volume":"37","author":"Han","year":"2014","journal-title":"Sleep"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5325","DOI":"10.1021\/acs.analchem.1c05212","article-title":"Deep Single-Cell-Type Proteome Profiling of Mouse Brain by Nonsurgical AAV-Mediated Proximity Labeling","volume":"94","author":"Sun","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/ncponc1187","article-title":"Strategies for discovering novel cancer biomarkers through utilization of emerging technologies","volume":"5","author":"Kulasingam","year":"2008","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_10","first-page":"1160","article-title":"Proteomics for cancer biomarker discovery","volume":"48","author":"Srinivas","year":"2002","journal-title":"Clin. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s41664-021-00197-6","article-title":"Mass Spectrometry-based Proteomics and Glycoproteomics in COVID-19 Biomarkers Identification: A Mini-review","volume":"5","author":"Zhong","year":"2021","journal-title":"J. Anal. Test"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1002\/elps.201800272","article-title":"Advances in mass spectrometry-based glycoproteomics","volume":"39","author":"Yu","year":"2018","journal-title":"Electrophoresis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.cbpa.2013.07.018","article-title":"High sensitivity capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry for the rapid analysis of complex proteomes","volume":"17","author":"Sun","year":"2013","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/prca.201400113","article-title":"Capillary zone electrophoresis on-line coupled to mass spectrometry: A perspective application for clinical proteomics","volume":"9","author":"Pejchinovski","year":"2015","journal-title":"Proteom. Clin. Appl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 variants, spike mutations and immune escape","volume":"19","author":"Harvey","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/1099-0801(200010)14:6<422::AID-BMC25>3.0.CO;2-I","article-title":"High-throughput quantitative bioanalysis by LC\/MS\/MS","volume":"14","author":"Jemal","year":"2000","journal-title":"Biomed Chromatogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jprot.2012.11.005","article-title":"Selectivity of LC-MS\/MS analysis: Implication for proteomics experiments","volume":"81","author":"Gallien","year":"2013","journal-title":"J. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.clinbiochem.2021.01.009","article-title":"Orexin-A measurement in narcolepsy: A stability study and a comparison of LC-MS\/MS and immunoassays","volume":"90","author":"Schinkelshoek","year":"2021","journal-title":"Clin. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1600478","DOI":"10.1002\/pmic.201600478","article-title":"Proteomic profiling of the hypothalamus in two mouse models of narcolepsy","volume":"17","author":"Azzam","year":"2017","journal-title":"Proteomics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.5664\/jcsm.4050","article-title":"Alcohol and NREM parasomnias: Evidence versus opinions in the international classification of sleep disorders, 3rd edition","volume":"10","author":"Cartwright","year":"2014","journal-title":"J. Clin. Sleep Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1710","DOI":"10.1212\/WNL.0000000000006439","article-title":"Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach","volume":"91","author":"Mondello","year":"2018","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2147\/NSS.S311801","article-title":"Searching for Novel Candidate Biomarkers of RLS in Blood by Proteomic Analysis","volume":"13","author":"Mondello","year":"2021","journal-title":"Nat. Sci. Sleep"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104680","DOI":"10.1016\/j.jprot.2022.104680","article-title":"Quantitative label-free proteomic analysis of human follicle fluid to identify novel candidate protein biomarker for endometriosis-associated infertility","volume":"266","author":"Cao","year":"2022","journal-title":"J. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/prot.21018","article-title":"Prediction of protein subcellular localization","volume":"64","author":"Yu","year":"2006","journal-title":"Proteins"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W585","DOI":"10.1093\/nar\/gkm259","article-title":"WoLF PSORT: Protein localization predictor","volume":"35","author":"Horton","year":"2007","journal-title":"Nucleic. Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28566","DOI":"10.3390\/ijms161226120","article-title":"Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry","volume":"16","author":"Rauniyar","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gutierrez Reyes, C.D., Huang, Y., Atashi, M., Zhang, J., Zhu, J., Liu, S., Parikh, N.D., Singal, A.G., Dai, J., and Lubman, D.M. (2021). PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma. Metabolites, 11.","DOI":"10.21203\/rs.3.rs-399869\/v1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1002\/pmic.201400364","article-title":"LC-MS\/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma","volume":"15","author":"Tsai","year":"2015","journal-title":"Proteomics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1466-8238.2011.00683.x","article-title":"Insights into the area under the receiver operating characteristic curve (AUC) as a discrimination measure in species distribution modelling","volume":"21","year":"2012","journal-title":"Glob. Ecol. Biogeogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fendo.2020.00145","article-title":"Role of Brown Adipose Tissue in Adiposity Associated With Narcolepsy Type 1","volume":"11","author":"Straat","year":"2020","journal-title":"Front Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s40263-017-0464-6","article-title":"Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment","volume":"31","author":"Barateau","year":"2017","journal-title":"CNS Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1017\/neu.2021.42","article-title":"Classical complement pathway factor alterations in narcolepsy","volume":"34","author":"Dursun","year":"2022","journal-title":"Acta Neuropsychiatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/0167-5699(93)90244-F","article-title":"Defining criteria for autoimmune diseases (Witebsky\u2019s postulates revisited)","volume":"14","author":"Rose","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41586-018-0540-1","article-title":"T cells in patients with narcolepsy target self-antigens of hypocretin neurons","volume":"562","author":"Latorre","year":"2018","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2147\/NSS.S275931","article-title":"Reviewing the Clinical Implications of Treating Narcolepsy as an Autoimmune Disorder","volume":"13","author":"Giannoccaro","year":"2021","journal-title":"Nat. Sci. Sleep"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00216-014-8341-3","article-title":"Bipolar disorder: Recent advances and future trends in bioanalytical developments for biomarker discovery","volume":"407","author":"Galazzi","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/elps.200900286","article-title":"High-abundance protein depletion: Comparison of methods for human plasma biomarker discovery","volume":"31","author":"Polaskova","year":"2010","journal-title":"Electrophoresis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s12274-014-0599-4","article-title":"Novel nanocomposites based on a strawberry-like gold-coated magnetite (Fe@Au) for protein separation in multiple myeloma serum samples","volume":"8","author":"Lodeiro","year":"2015","journal-title":"Nano Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, J., Tong, L., Lin, G., Wang, H., Zhang, L., and Yang, X. (2020). Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07436-6"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.18632\/aging.204048","article-title":"The immune regulation of BCL3 in glioblastoma with mutated IDH1","volume":"14","author":"Fan","year":"2022","journal-title":"Aging Albany N. Y."},{"key":"ref_42","first-page":"9022700","article-title":"Identification of Key Genes in Nasopharyngeal Carcinoma Based on Bioinformatics Analysis","volume":"2022","author":"Song","year":"2022","journal-title":"Comput. Intell. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1111\/cns.13956","article-title":"Glioma stem cell signature predicts the prognosis and the response to tumor treating fields treatment","volume":"28","author":"Chen","year":"2022","journal-title":"CNS Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mogavero, M.P., Silvani, A., DelRosso, L.M., Salemi, M., and Ferri, R. (2021). Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity. Cancers, 13.","DOI":"10.3390\/cancers13112612"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127-22","DOI":"10.4049\/jimmunol.202.Supp.127.22","article-title":"Neutrophil maturation and their response to infectious pathogens are regulated by microbiota","volume":"202","author":"Gadjeva","year":"2019","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fnbeh.2013.00028","article-title":"Role of orexin in modulating arousal, feeding, and motivation","volume":"7","author":"Tsujino","year":"2013","journal-title":"Front. Behav. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00125-008-0929-8","article-title":"Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice","volume":"51","author":"Tsuneki","year":"2008","journal-title":"Diabetologia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/MCP.0000000000000426","article-title":"Autoimmunity in narcolepsy","volume":"23","author":"Bonvalet","year":"2017","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_49","unstructured":"Berczi, I. (2016). Insights to Neuroimmune Biology, Elsevier. [2nd ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110003","DOI":"10.1016\/j.cellsig.2021.110003","article-title":"Regulators and signalling in insect antimicrobial innate immunity: Functional molecules and cellular pathways","volume":"83","author":"Zhang","year":"2021","journal-title":"Cell Signal"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000329999","article-title":"Role of p53 in neurodegenerative diseases","volume":"9","author":"Chang","year":"2012","journal-title":"Neuro-Degener. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1097\/BOR.0000000000000633","article-title":"Complement, infection, and autoimmunity","volume":"31","author":"Conigliaro","year":"2019","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mogavero, M.P., DelRosso, L.M., Bruni, O., Salemi, M., Salsone, M., Novellino, F., Zucconi, M., Ferini Strambi, L., and Ferri, R. (2023). Genetics and Epigenetics of Rare Hypersomnia. A Possible Keystone for their Diagnosis and Treatment within the Framework of Precision Medicine. Trends Genet. TIG, in press.","DOI":"10.1016\/j.tig.2023.02.003"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/3\/420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:40:29Z","timestamp":1760121629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/3\/420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["biom13030420"],"URL":"https:\/\/doi.org\/10.3390\/biom13030420","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]}}}