Neuroscience & Biobehavioral Reviews, Год журнала: 2021, Номер 129, С. 157 - 179
Опубликована: Июнь 29, 2021
Язык: Английский
Nature Reviews Neurology, Год журнала: 2021, Номер 18(1), С. 7 - 24
Опубликована: Ноя. 10, 2021
Язык: Английский
Процитировано
162
Journal of Internal Medicine, Год журнала: 2022, Номер 291(5), С. 533 - 556
Опубликована: Янв. 19, 2022
Abstract The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on specific receptors that widely distributed across brain and involved a myriad of neurophysiological functions include sleep, arousal, feeding, reward, fear, anxiety cognition. Hcrt cell loss humans leads to narcolepsy with cataplexy (narcolepsy type 1), disorder characterized by intrusions sleep into wakefulness, demonstrating system is nonredundant essential for sleep/wake stability. causal link between Hcrts arousal/wakefulness stabilisation has led development new class drugs, receptor antagonists treat insomnia, based assumption blocking orexin‐induced arousal will facilitate sleep. This been clinically validated: currently, approved insomnia (suvorexant lemborexant), New Drug Application recently submitted US Food Administration third drug (daridorexant). Other therapeutic applications under investigation reduction cravings substance‐use disorders prevention neurodegenerative such Alzheimer's disease, given apparent bidirectional relationship poor worsening disease. Circuit neuroscience findings suggest hub integrates diverse inputs modulating (e.g., circadian rhythms, metabolic status, positive negative emotions) conveys this information multiple output regions. neuronal architecture explains wealth physiological associated highlights potential target number disorders. We discuss present future possible drugs targeting treatment circuit‐related neuropsychiatric conditions.
Язык: Английский
Процитировано
73
Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)
Опубликована: Фев. 13, 2023
Abstract Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions diseases. Circadian disruption disorders aggravate neurodegeneration in turn disrupt sleep. Importantly, various increase the risk Thus, harnessing biology findings from preclinical translational research is importance for reducing improving symptoms quality life individuals with via approaches that normalize context precision medicine. In this review, we discuss implications by summarizing both human animal studies, focusing on links prevalent forms neurodegeneration. These provide valuable insights into pathogenesis suggest promising role circadian-based interventions.
Язык: Английский
Процитировано
65
Neurobiology of Disease, Год журнала: 2020, Номер 144, С. 105031 - 105031
Опубликована: Июль 29, 2020
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an asymptomatic period of amyloid-β (Aβ) deposition as insoluble extracellular plaque, intracellular tau aggregation, neuronal and synaptic loss, subsequent cognitive dysfunction dementia. A growing public health crisis, the worldwide prevalence AD expected to rise from 46.8 million individuals affected in 2015 131.5 2050. Sleep disturbances have been associated with increased future risk AD. bi-directional relationship hypothesized between sleep either markers for pathology and/or mechanism mediating In this review, evidence humans supporting complex will be discussed well therapeutic potential challenges treating prevent or delay onset
Язык: Английский
Процитировано
108
Acta Pharmacologica Sinica, Год журнала: 2020, Номер 42(9), С. 1382 - 1389
Опубликована: Дек. 2, 2020
Язык: Английский
Процитировано
73
Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)
Опубликована: Апрель 21, 2023
Abstract Failed proteostasis is a well-documented feature of Alzheimer’s disease, particularly, reduced protein degradation and clearance. However, the contribution failed to neuronal circuit dysfunction an emerging concept in neurodegenerative research will prove critical understanding cognitive decline. Our objective convey disease progression with growing evidence for bidirectional relationship sleep disruption failure. Proteostasis tauopathy disrupts neurons that regulate sleep–wake cycle, which presents behavior as impaired slow wave rapid eye movement patterns. Subsequent loss further impairs Sleep defined seen early many disorders contributes memory impairments disease. Canonical pathological hallmarks, β-amyloid, tau, directly disrupt sleep, neurodegeneration locus coeruleus, hippocampal hypothalamic from tau proteinopathy causes circuitry sleep. Acting positive-feedback-loop, circadian rhythm then increase spread β-amyloid through proteasome, autophagy, unfolded response glymphatic This phenomenon extends beyond interactions impairment homeostasis TDP-43, α-synuclein, FUS, huntingtin proteins, implicating important consideration array diseases cases mixed neuropathology. Critically, dynamics this interaction environment are not fully elucidated deserving discussion research. Finally, we propose sleep-enhancing therapeutics potential interventions promoting healthy proteostasis, including clearance, mechanistically linking these processes. With clinical preclinical research, dynamic diagnostic therapeutic framework, informing precise single- combinatorial-treatments other brain disorders. Graphical
Язык: Английский
Процитировано
27
The Annual Review of Pharmacology and Toxicology, Год журнала: 2023, Номер 64(1), С. 359 - 386
Опубликована: Сен. 14, 2023
Sleep is essential for human well-being, yet the quality and quantity of sleep reduce as age advances. Older persons (>65 years old) are more at risk disorders accompanied and/or exacerbated by poor sleep. Furthermore, evidence supports a bidirectional relationship between disrupted Alzheimer's disease (AD) or related dementias. Orexin/hypocretin neuropeptides stabilize wakefulness, several orexin receptor antagonists (ORAs) approved treatment insomnia in adults. Dysregulation system occurs aging AD, positioning ORAs advantageous these populations. Indeed, clinical studies indicate that efficacious hypnotics older dementia patients and, adults, generally well tolerated. likely to be effective when administered early sleep/wake dysregulation reestablish good sleep/wake-related behaviors accumulation dementia-associated proteinopathic substrates. Improving represents tremendous opportunity benefit patients, caregivers, health systems.
Язык: Английский
Процитировано
16
Journal of Neuroscience, Год журнала: 2023, Номер 43(25), С. 4738 - 4749
Опубликована: Май 25, 2023
The impact of tau pathology on sleep microarchitecture features, including slow oscillations, spindles, and their coupling, has been understudied, despite the proposed importance these electrophysiological features toward learning memory. Dual orexin receptor antagonists (DORAs) are known to promote sleep, but whether how they affect in setting tauopathy is unknown. In PS19 mouse model MAPT (microtubule-associated protein tau) P301S (both male female), young mice 2–3 months old show a electrophysiology signature with markedly reduced spindle duration power elevated oscillation (SO) density compared littermate controls, although there no significant hyperphosphorylation, tangle formation, or neurodegeneration at this age. With aging, evidence for disruption mice, characterized by REM duration, increased non-REM fragmentation, more frequent brief arousals macrolevel density, SO spindle-SO coupling microlevel. ∼33% aged we unexpectedly observed abnormal goal-directed behaviors REM, mastication, paw grasp, forelimb/hindlimb extension, seemingly consistent behavior disorder (RBD). Oral administration DORA-12 albeit shorter bout lengths, without change spindle–SO either bands, arousal index. We effect objective measures RBD, thereby encouraging future exploration DORA effects sleep-mediated cognition RBD treatment. SIGNIFICANCE STATEMENT specific macroarchitecture throughout aging remains Our key findings include following: (1) identification EEG constituting an early biomarker impending tauopathy; (2) physiology deteriorates that also markers off-line cognitive processing; (3) novel observation dream enactment reminiscent occur, likely first such model; (4) dual antagonist capable restoring several abnormalities.
Язык: Английский
Процитировано
15
Frontiers in Medicine, Год журнала: 2023, Номер 9
Опубликована: Фев. 1, 2023
Orexin is a neuropeptide produced by the lateral hypothalamus that plays an important role in regulating sleep-wake cycle. The overexpression of orexinergic system may be related to pathology sleep/wakefulness disorders Alzheimer's disease (AD). In AD patients, increase cerebrospinal fluid orexin levels associated with parallel sleep deterioration. Dual receptor antagonist (DORA) can not only treat sleep-wakefulness disorder but also improve performance patients cognitive behavior disorder. It critical clarify AD, study its relationship decline and evaluate safety efficacy DORA.
Язык: Английский
Процитировано
13
Neurological Sciences, Год журнала: 2023, Номер 45(2), С. 749 - 767
Опубликована: Дек. 12, 2023
Язык: Английский
Процитировано
13