Melodie Bonvalet1, Hanna M Ollila, Aditya Ambati, Emmanuel Mignot. 1. aDepartment of Psychiatry and Behavioral Sciences, Center for Sleep Sciences, Stanford University School of Medicine, Palo Alto, California, USA bNational Institute for Health and Welfare, Public Genomics Unit cInstitute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
Abstract
PURPOSE OF REVIEW: Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. RECENT FINDINGS: Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. SUMMARY: Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development.
PURPOSE OF REVIEW: Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. RECENT FINDINGS: Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. SUMMARY:Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development.
Authors: Astrid van der Heide; Ingrid M Hegeman-Kleinn; Els Peeters; Gert J Lammers; Rolf Fronczek Journal: J Neuroimmunol Date: 2015-04-28 Impact factor: 3.478
Authors: Arash Zandian; Björn Forsström; Anna Häggmark-Månberg; Jochen M Schwenk; Mathias Uhlén; Peter Nilsson; Burcu Ayoglu Journal: J Proteome Res Date: 2017-02-09 Impact factor: 4.466
Authors: Syed Sohail Ahmed; Wayne Volkmuth; José Duca; Lorenzo Corti; Michele Pallaoro; Alfredo Pezzicoli; Anette Karle; Fabio Rigat; Rino Rappuoli; Vas Narasimhan; Ilkka Julkunen; Arja Vuorela; Outi Vaarala; Hanna Nohynek; Franco Laghi Pasini; Emanuele Montomoli; Claudia Trombetta; Christopher M Adams; Jonathan Rothbard; Lawrence Steinman Journal: Sci Transl Med Date: 2015-07-01 Impact factor: 17.956
Authors: Juliette Faraco; Ling Lin; Birgitte Rahbek Kornum; Eimear E Kenny; Gosia Trynka; Mali Einen; Tom J Rico; Peter Lichtner; Yves Dauvilliers; Isabelle Arnulf; Michel Lecendreux; Sirous Javidi; Peter Geisler; Geert Mayer; Fabio Pizza; Francesca Poli; Giuseppe Plazzi; Sebastiaan Overeem; Gert Jan Lammers; David Kemlink; Karel Sonka; Sona Nevsimalova; Guy Rouleau; Alex Desautels; Jacques Montplaisir; Birgit Frauscher; Laura Ehrmann; Birgit Högl; Poul Jennum; Patrice Bourgin; Rosa Peraita-Adrados; Alex Iranzo; Claudio Bassetti; Wei-Min Chen; Patrick Concannon; Susan D Thompson; Vincent Damotte; Bertrand Fontaine; Maxime Breban; Christian Gieger; Norman Klopp; Panos Deloukas; Cisca Wijmenga; Joachim Hallmayer; Suna Onengut-Gumuscu; Stephen S Rich; Juliane Winkelmann; Emmanuel Mignot Journal: PLoS Genet Date: 2013-02-14 Impact factor: 5.917
Authors: Helle Sadam; Arno Pihlak; Anri Kivil; Susan Pihelgas; Mariliis Jaago; Priit Adler; Jaak Vilo; Olli Vapalahti; Toomas Neuman; Dan Lindholm; Markku Partinen; Antti Vaheri; Kaia Palm Journal: EBioMedicine Date: 2018-02-02 Impact factor: 8.143
Authors: Zina-Mary Manjaly; Neil A Harrison; Hugo D Critchley; Cao Tri Do; Gabor Stefanics; Nicole Wenderoth; Andreas Lutterotti; Alfred Müller; Klaas Enno Stephan Journal: J Neurol Neurosurg Psychiatry Date: 2019-01-25 Impact factor: 10.154