{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:45:18Z","timestamp":1773297918797,"version":"3.50.1"},"reference-count":25,"publisher":"Danish Medical Association","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ugeskr L\u00e6ger"],"abstract":"<jats:p>Narcolepsy is a neurological sleep disorder characterized by a disrupted sleep-wake cycle. The disorder is subdivided into type 1 (NT1) and type 2, where NT1 is distinguished by cataplexy and low hypocretin levels in the cerebrospinal fluid. Despite lacking indisputable evidence, the scientific consensus regarding the disease pathogenesis revolves around an autoimmune destruction of the hypocretin neurons. This is now being challenged by a study proposing that NT1 instead stems from an epigenetic silencing of the hypocretin gene, suggesting reversibility and thereby having profound implications, as pointed out in this review.<\/jats:p>","DOI":"10.61409\/v09240580","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T01:31:12Z","timestamp":1740706272000},"page":"1-9","source":"Crossref","is-referenced-by-count":1,"title":["Narcolepsy type 1 and hypocretin neurons"],"prefix":"10.61409","author":[{"given":"Hassan Ali","family":"Maanaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stine","family":"Knudsen-Heier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte Rahbek","family":"Kornum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"40208","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"ref0","unstructured":"Knudsen S, Jennum PJ. Narkolepsi - nye molekyl\u00e6rbiologiske landvindinger. Ugeskr L\u00e6ger. 2006;168:3699-704"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Knudsen S, Jennum PJ, Alving J et al. Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population. Sleep. 2010;33(2):169-76. https:\/\/doi.org\/10.1093\/sleep\/33.2.169","DOI":"10.1093\/sleep\/33.2.169"},{"key":"ref2","unstructured":"Ovesen J, Kjeldsen HC. I: L\u00e6geh\u00e5ndbogen. Narkolepsi. 2022. www.sundhed.dk\/sundhedsfaglig\/laegehaandbogen\/oere-naese-hals\/tilstande-og-sygdomme\/soevn\/narkolepsi\/ (30. mar 2024)"},{"key":"ref3","unstructured":"American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. 2014."},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437(7063):1257-63. https:\/\/doi.org\/10.1038\/nature04284","DOI":"10.1038\/nature04284"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Pizza F, Barateau L, Dauvilliers Y, Plazzi G. The orexin story, sleep and sleep disturbances. J Sleep Res. 2022;31(4):e13665. https:\/\/doi.org\/10.1111\/jsr.13665","DOI":"10.1111\/jsr.13665"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Bassetti CLA, Kallweit U, Vignatelli L et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res. 2021;30(6):e13387. https:\/\/doi.org\/10.1111\/jsr.13387","DOI":"10.1111\/jsr.13387"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Kornum BR, Knudsen S, Ollila HM et al. Narcolepsy. Nat Rev Dis Primers. 2017;3(1):16100. https:\/\/doi.org\/10.1038\/nrdp.2016.100","DOI":"10.1038\/nrdp.2016.100"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Liblau RS, Latorre D, Kornum BR et al. The immunopathogenesis of narcolepsy type 1. Nat Rev Immunol. 2024;24(1):33-48. https:\/\/doi.org\/10.1038\/s41577-023-00902-9","DOI":"10.1038\/s41577-023-00902-9"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Kornum BR. Narcolepsy type 1: what have we learned from immunology? Sleep. 2020;43(10):zsaa055. https:\/\/doi.org\/10.1093\/sleep\/zsaa055","DOI":"10.1093\/sleep\/zsaa055"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Seifinejad A, Ramosaj M, Shan L et al. Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy. Proc Natl Acad Sci U S A. 2023;120(19):e2220911120. https:\/\/doi.org\/10.1073\/pnas.2220911120","DOI":"10.1073\/pnas.2220911120"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspective. 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Neurology. 2009;73(7):511-7. https:\/\/doi.org\/10.1212\/WNL.0b013e3181b2a6af","DOI":"10.1212\/WNL.0b013e3181b2a6af"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Thannickal TC, John J, Shan L et al. Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy. Sci Transl Med. 2018;10(447):eaao4953. https:\/\/doi.org\/10.1126\/scitranslmed.aao4953","DOI":"10.1126\/scitranslmed.aao4953"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Tabuchi S, Tsunematsu T, Black SW et al. Conditional ablation of orexin\/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J Neurosci. 2014;34(19):6495-509. https:\/\/doi.org\/10.1523\/JNEUROSCI.0073-14.2014","DOI":"10.1523\/JNEUROSCI.0073-14.2014"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"\u00c6gidius HM, Kruse L, Christensen GL et al. Pre-treatment of blood samples reveal normal blood hypocretin\/orexin signal in narcolepsy type 1. Brain Commun. 2021;3(2):fcab050. https:\/\/doi.org\/10.1093\/braincomms\/fcab050","DOI":"10.1093\/braincomms\/fcab050"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Torstensen EW, \u00d8sterby NCH, Pizza F et al. Repeated measures of hypocretin-1 in Danish and Italian patients with narcolepsy and in controls. Sleep Med. 2023;101:213-220. https:\/\/doi.org\/10.1016\/j.sleep.2022.10.004","DOI":"10.1016\/j.sleep.2022.10.004"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Lopez R, Doukkali A, Barateau L et al. Test-retest reliability of the multiple sleep latency test in central disorders of hypersomnolence. Sleep. 2017;40(12). https:\/\/doi.org\/10.1093\/sleep\/zsx164","DOI":"10.1093\/sleep\/zsx164"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Ruoff C, Pizza F, Trotti LM et al. 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