ArticleNature neuroscience2025
Lemborexant ameliorates tau-mediated sleep loss and neurodegeneration in males in a mouse model of tauopathy.
Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- The glymphatic-lymphatic axis: known pathways, open questions, and emerging roles in neurodegeneration.Translational neurodegeneration · 2026Review
- The default mode network exhibits circuit-specific selective vulnerability despite widespread amyloid burden in an animal model of Alzheimer's disease.Nature communications · 2026Article
- Refining our understanding of sleep impairment and connection to Alzheimer's disease in preclinical models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Protein kinase CK2α' as a dual modulator of neuroimmune signaling and synaptic dysfunction in tauopathy.Translational neurodegeneration · 2026Article
- Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice.Molecular neurodegeneration · 2026Article
- Dexmedetomidine improves sleep quality and alleviates emotional dysfunction by attenuating α-synuclein deposition in mice with sepsis-associated encephalopathy.Journal of advanced research · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Zolpidem restores sleep and decreases amyloid in a mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sleep disturbances and Alzheimer's disease: a multiscale approach from exposome to neurobiology and precision medicine.GeroScience · 2026Review
- Orexin Receptor Antagonism Improves Sleep Quality and Mitigates Lipopolysaccharide-Induced Inflammatory Responses in a Mouse Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Mass Spectrometry-Based Quantification of Orexin Species in Human Cerebrospinal Fluid Reveals Differential Dynamics Associated with Sleep.medRxiv : the preprint server for health sciences · 2025Article
- Lemborexant Reduces Infarct Volume and Improves Long-Term Functional Recovery in a Murine Model of Ischemic Stroke.bioRxiv : the preprint server for biology · 2025Article
- Protein kinase CK2α' as a dual modulator of immune signaling and synaptic dysfunction in Tauopathy.bioRxiv : the preprint server for biology · 2025Article
- Autophagic impairment in sleep-wake circuitry is linked to sleep loss at the early stages of Alzheimer's disease.Molecular neurodegeneration · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Sleep disturbances are associated with the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and primary tauopathies. Here we demonstrate that administration of the dual orexin receptor antagonist lemborexant in the P301S/E4 mouse model of tauopathy improves tau-associated impairments in sleep-wake behavior. It also protects against chronic reactive microgliosis and brain atrophy in male P301S/E4 mice by preventing abnormal phosphorylation of tau. These neuroprotective effects in males were not observed after administration of the nonorexinergic drug zolpidem that similarly promoted nonrapid eye movement sleep. Furthermore, both genetic ablation of orexin receptor 2 and lemborexant treatment reduced wakefulness and decreased seeding and spreading of phosphorylated tau in the brain of wild-type mice. These findings raise the therapeutic potential of targeting sleep by orexin receptor antagonism to prevent abnormal tau phosphorylation and limit tau-induced damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.