Universität zu Köln

Klein, G., Burghaus, L. and Diederich, N. (2012). Pathogenesis of Narcolepsy: From HLA Association to Hypocretin Deficiency. Forschritte Neurol. Psychiatr., 80 (11). S. 627 - 635. STUTTGART: GEORG THIEME VERLAG KG. ISSN 0720-4299

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Abstract

Narcolepsy is a rare and chronic sleep disorder, characterised by excessive daytime sleepiness. Frequently associated signs are cataplexy, sleep paralysis and hypnagogic or hypnopompic hallucinations. Advances in understanding the pathogenesis of the disease have essentially been elucidated during the last fifteen years. The most significant finding has been the discovery of hypocretin-1 and -2 in 1998. Hypocretin-containing cells have widespread projections throughout the entire CNS and play a crucial role in the regulation of the sleep-wake cycle. They also contribute to olefaction and to the regulation of food intake. Animal models and human studies concordantly show that the disturbed hypocretin system is the probable cause of narcolepsy. However, it remains unclear why there is neuronal death of hypocretin-producing cells in the lateral hypothalamus. As the HLA-allele DQB1*0602 is associated with narcolepsy and hypocretin deficiency, an autoimmune reaction against hypocretin-producing neurons has been vigorously discussed. Newly discovered gene polymorphisms as well as previously unknown pathogenetic mechanisms, linking the sleep-wake cycle with the immune system, may also contribute to the pathogenetic cascade. Worthy of mention in this context is, e. g., the insulin-like growth factor-binding protein 3 (IGFBP3), whose overexpression causes a down-regulation of the hypocretin production. Substitution of the deficient neuropeptides by hypocretin agonists may become the causal treatment strategy of the future, if an adequate administration route can be found. Presently, animal trials, including genetic therapy, cell transplantations or the administration of hypocretin receptor agonists, are underway.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burghaus, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diederich, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-479527
DOI:	10.1055/s-0031-1299447
Journal or Publication Title:	Forschritte Neurol. Psychiatr.
Volume:	80
Number:	11
Page Range:	S. 627 - 635
Date:	2012
Publisher:	GEORG THIEME VERLAG KG
Place of Publication:	STUTTGART
ISSN:	0720-4299
Language:	German
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OREXIN-A HYPOCRETIN-1; NECROSIS-FACTOR-ALPHA; RECEPTOR AUTORADIOGRAPHY; CLINICAL-FEATURES; CANINE NARCOLEPSY; SLEEP-DISORDERS; PLASMA-LEVELS; REM-SLEEP; CATAPLEXY; ONSET Multiple languages Clinical Neurology; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47952