Hypocretins (orexins): The ultimate translational neuropeptides

  title={Hypocretins (orexins): The ultimate translational neuropeptides},
  author={Laura H. Jacobson and Daniel Hoyer and Luis de Lecea},
  journal={Journal of Internal Medicine},
  pages={533 - 556}
The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on two specific receptors that are widely distributed across the brain and involved in a myriad of neurophysiological functions that include sleep, arousal, feeding, reward, fear, anxiety and cognition. Hcrt cell loss in humans leads to narcolepsy with cataplexy (narcolepsy type 1), a disorder characterized by intrusions of sleep into wakefulness, demonstrating that… 

The Orexin receptors: Structural and anti-tumoral properties

The identification of OX1R expression in digestive cancers encompassing colon, pancreas and liver cancers and its ability to trigger mitochondrial apoptosis in tumoral cells, indicate a new putative therapeutical action of orexins and paradoxically OXR antagonists.

Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation

The current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management are described and recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are highlighted.

The neuropeptide landscape of human prefrontal cortex

  • Wen ZhongS. Barde T. Hökfelt
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2022
The results suggest that the well-established anatomical and functional heterogeneity of human PFC is also reflected in the expression pattern of the neuropeptides.

Neuromodulatory and Protective Effects Induced by the Association of Herbal Extracts from Valeriana officinalis, Ziziphus jujuba, and Humulus lupulus with Melatonin: An Innovative Formulation for Counteracting Sleep Disorders

The biological effects of melatonin and herbal extracts with phytotherapy interest in V. officinalis, Z. jujuba, and H. lupulus demonstrated their intrinsic scavenging/reducing activity, together with protective and neuromodulatory effects in the hypothalamus, with a significant reduction of both orexin A gene expression and serotonin steady state level.



Behavioral Neuroscience of Orexin/Hypocretin

The orexin/hypocretin receptor coordinates, now available to the broader academic and drug discovery community, will facilitate rational design of new therapeutics that modulate orexIn/ hypocretin signaling in humans.

Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy

It is shown that orexin delivered via intrathecal route at the lumbar level significantly inhibited narcoleptic symptoms in mice without altering sleep/wake profile, indicating the possibility that oRexin can be delivered intrathecally in humans, using an implantable, refillable, and programmable miniature pump to treat narcoLEpsy.

The Discovery of Suvorexant, the First Orexin Receptor Drug for Insomnia.

Among DORAs evaluated clinically, suvorexant has pharmacokinetic properties engineered for a plasma half-life appropriate for rapid sleep onset and maintenance at low to moderate doses, and the preservation of cognitive performance and the ability to arouse to salient stimuli after DORA administration suggest further advantages over historical therapies.

Orexin/hypocretin role in reward: implications for opioid and other addictions

This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction‐related behaviours and propose novel hypotheses for the mechanisms by which orexIn signalling may impart drug seeking.

Recent advances in understanding the roles of hypocretin/orexin in arousal, affect, and motivation

Recent advances in the neurobiology of hypocretins are reviewed, surveying findings on Hcrt function within normal sleep/wake states as well as situations of aberrant sleep (that is, narcolepsy).

Orexin Receptor Antagonists

It is proposed that REM sleep enhancement by DORAs may provide opportunities to treat specific neurological disorders and OX2R antagonists such as seltorexant may have broader applications as they appear to promote balanced sleep architecture in preclinical models and should, in theory, have a lower narcoleptic/cataplectic potential.