Article
Pharmacology & Pharmacy
Tzu-Ling Li, Yen-Hsien Lee, Feng-Hsu Wu, Ling-Ling Hwang
Summary: Orexin-A directly excites over half of DMH neurons, including those innervating the RVLM, through decreasing K+ conductance, activating NCX, and/or increasing NSCC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Marieke Vringer, Birgitte Rahbek Kornum
Summary: Narcolepsy type 1 and type 2 are characterized by excessive daytime sleepiness and reduced quality of life, with current treatments focused on improving daytime sleepiness and reducing cataplexy. Targeting Hcrt receptors shows promise in alleviating symptoms, but careful consideration of potential side effects is required. Immunotherapies may target the core pathophysiology of narcolepsy, but further research is needed to identify the optimal therapeutic target.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Cardiac & Cardiovascular Systems
Peter Wohlfahrt, Dominik Jenca, Vojtech Melenovsky, Petr Jarolim, Dana Dlouha, Marek Sramko, Martin Kotrc, Michael Zelizko, Jolana Mrazkova, Jan Pitha, Vera Adamkova, Josef Kautzner
Summary: The lack of hypocretin/orexin signaling is associated with increased mortality risk after myocardial infarction (MI). The allele variant that attenuates this signaling is associated with a higher risk of death after MI.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Clinical Neurology
Maria P. Mogavero, Alessandro Silvani, Giuseppe Lanza, Lourdes M. DelRosso, Luigi Ferini-Strambi, Raffaele Ferri
Summary: After describing orexins and their roles in sleep and medical disorders, the article discusses the clinical evidence on the effects of DORAs and SORAs on insomnia to provide recommendations for further assessment in personalized and precision medicine. Trials with orexin receptor antagonists have shown potential as a valid therapeutic option for insomnia in various medical conditions, but more studies are needed to determine the most suitable options for different patient populations.
NATURE AND SCIENCE OF SLEEP
(2023)
Editorial Material
Neurosciences
Jacqueline B. Mehr, Michelle M. Bilotti, Morgan H. James
Summary: This article discusses how the hypothalamic orexin system is now linked with motivated behavior and becomes overactive in addicted states, offering potential therapeutic opportunities for substance use disorders based on normalizing orexin function.
TRENDS IN NEUROSCIENCES
(2021)
Article
Cell Biology
Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Summary: This study examined the use of a dual-orexin receptor antagonist in opioid withdrawal and found that it may have potential benefits for improving sleep and withdrawal outcomes.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Clinical Neurology
Chiara Berteotti, Carmen Calvello, Claudio Liguori
Summary: Epilepsy is a common neurological disorder that affects patients of all ages and is associated with reduced quality of life and comorbidities. Sleep impairment is frequently observed in epilepsy patients, and the relationship between sleep and epilepsy is bidirectional. The orexin system, which plays a role in controlling the sleep-wake cycle, may be affected in epilepsy patients. Clinical studies have shown inconsistent results due to different methodologies in quantifying orexin levels. Dual orexin receptor antagonists (DORAs) have been suggested as a potential treatment for sleep impairment and insomnia in epilepsy patients.
Article
Clinical Neurology
Brendan P. Lucey, Haiyan Liu, Cristina D. Toedebusch, David Freund, Tiara Redrick, Samir L. Chahin, Kwasi G. Mawuenyega, James G. Bollinger, Vitaliy Ovod, Nicolas R. Barthelemy, Randall J. Bateman
Summary: In this study, it was found that suvorexant, a dual orexin receptor antagonist, acutely decreased tau phosphorylation and amyloid-beta concentrations in the central nervous system. This suggests that suvorexant may have potential as a repurposed drug for the prevention of Alzheimer's disease.
ANNALS OF NEUROLOGY
(2023)
Article
Psychiatry
Jing Lu, Man-Li Huang, Jin-Hui Li, Kang-Yu Jin, Hai-Mei Li, Ting-Ting Mou, Rolf Fronczek, Jin-Feng Duan, Wei-Juan Xu, Dick Swaab, Ai-Min Bao
Summary: Research indicates decreased central hypocretin neurotransmission in schizophrenia patients, especially females. Plasma hypocretin-1 levels were significantly lower in schizophrenia patients, with female patients showing a more significant decrease. Hypothalamic hypocretin-1 ir also decreased in schizophrenia patients, primarily in females, while male patients showed changes in Hcrt-R mRNA expression.
SCHIZOPHRENIA BULLETIN
(2021)
Article
Clinical Neurology
Silvia Melzi, Anne-Laure Morel, Celine Scote-Blachon, Roland Liblau, Yves Dauvilliers, Christelle Peyron
Summary: The study found that in mouse models, the expression levels of histamine and noradrenaline, two wake-promoting systems, are not regulated by orexin levels, whether orexin deficiency is constitutive or induced at adult age. It also showed that there was no recruitment of histamine by local neuroinflammation. Further research is needed to define the role of histamine in the pathophysiology of narcolepsy type 1.
Article
Multidisciplinary Sciences
Shi-Bin Li, Valentina Martinez Damonte, Chong Chen, Gordon X. Wang, Justus M. Kebschull, Hiroshi Yamaguchi, Wen-Jie Bian, Carolin Purmann, Reenal Pattni, Alexander Eckehart Urban, Philippe Mourrain, Julie A. Kauer, Gregory Scherrer, Luis de Lecea
Summary: Sleep quality declines with age and this study identified hyperexcitable hypocretin/orexin (Hcrt/OX) neurons as drivers of sleep fragmentation during aging. Activation of Hcrt neurons increased wakefulness and aged Hcrt neurons showed hyperexcitability and impaired M-current. Disruption of Kcnq2/3 genes in young mice led to sleep destabilization resembling aging-associated sleep fragmentation.
Article
Neurosciences
Jazmine D. W. Yaeger, Kevin T. Krupp, Benjamin M. Jacobs, Benard O. Onserio, Brandon L. Meyerink, Jacob T. Cain, Patrick J. Ronan, Kenneth J. Renner, Ralph J. DiLeone, Cliff H. Summers
Summary: This study investigates the role of Orx1 receptors in stress-induced phenotypes in mice and finds that antagonism of Orx1 receptors can modulate behavioral responses and lead to reorganization of gene expression, providing evidence for a receptor-driven mechanism that balances stress and anti-stress responses.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Anja Holm, Marie-Laure Possovre, Mojtaba Bandarabadi, Kristine F. Moseholm, Jessica L. Justinussen, Ivan Bozic, Rene Lemcke, Yoan Arribat, Francesca Amati, Asli Silahtaroglu, Maxime Juventin, Antoine Adamantidis, Mehdi Tafti, Birgitte R. Kornum
Summary: This study found that miR-137 regulates sleep-wake states by targeting the Hcrt gene. Inhibition of miR-137 increases Hcrt expression and prolongs wakefulness, and this interaction is evolutionarily conserved in different species. Additionally, the study showed that miR-137 expression is regulated by IL-13, and Hcrt gene expression is regulated by miR-137.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Clinical Neurology
Jari K. Gool, Eva M. van Heese, Mink S. Schinkelshoek, Aniek Remmerswaal, Gert Jan Lammers, Karin D. van Dijk, Rolf Fronczek
Summary: This study assessed the effect of opioid use on narcolepsy type 1 symptom severity through a literature review and questionnaire study. The results showed that opioids could improve narcolepsy symptom severity, with the most significant improvements seen in sleep quality and excessive daytime sleepiness.
Review
Chemistry, Multidisciplinary
Pilar Marcos, Rafael Covenas
Summary: Peptides play a role in tumor cell mitogenesis and migration, with overexpression of peptide receptors in cancer cells. This review discusses the involvement of the orexinergic system in thirteen cancer types, showing its upregulation in many tumors and its dual effect on apoptosis and proliferation. OXR antagonists or agonists have potential as antitumor agents. The review also explores the complexities of the orexigenic system and its potential therapeutic applications, including dimerization/oligomerization of OXRs, epigenetic mechanisms, biomarkers, combination therapy, and anti-inflammatory effects mediated by orexins.
APPLIED SCIENCES-BASEL
(2023)