Evidence map›Paper›PMID 26223541›Full record

ArticleScientific reports2015

Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103.

Julie Davies, Jing Chen, Ryan Pink, David Carter, Nigel Saunders, Georgios Sotiriadis, Bo Bai, Yanyou Pan, David Howlett, Annette Payne and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 74 citations in OpenAlex.

  1. Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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  10. Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Relationship betweenInternational journal of environmental research and public health · 2023
    Article
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  13. Review
  14. Article
  15. Article
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  17. Article
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  20. Hypocretin (Orexin) Replacement Therapies.Medicine in drug discovery · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Julie DaviesBiosciences, College of Health and Life Sciences, Brunel University, Uxbridge, UB8 3PH, UK.
Jing Chen1] Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK [2] Neurobiology Institute, Jining Medical University, Jining, Shandong, 272067, P.R. China.
Ryan PinkDepartment of Biological and Medical Sciences, Oxford Brookes University, UK.
David CarterDepartment of Biological and Medical Sciences, Oxford Brookes University, UK.
Nigel SaundersCentre for Systems and Synthetic Biology, Brunel University, Uxbridge UB83PH, UK.
Georgios SotiriadisBiosciences, College of Health and Life Sciences, Brunel University, Uxbridge, UB8 3PH, UK.
Bo BaiNeurobiology Institute, Jining Medical University, Jining, Shandong, 272067, P.R. China.
Yanyou PanNeurobiology Institute, Jining Medical University, Jining, Shandong, 272067, P.R. China.
David HowlettWolfson Centre for Age Related Diseases, King's College London, London, SE11UL, UK.
Annette PayneDepartment of Computer Science, College of Engineering, Design and Physical Sciences, Brunel University, Uxbridge UB8 3PH, UK.
Harpal Randeva1] Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK [2] Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, B4 7ET, UK.
Emmanouil KarterisBiosciences, College of Health and Life Sciences, Brunel University, Uxbridge, UB8 3PH, UK.
Brunel University of London · GBJining Medical University · CNOxford Brookes University · GBAston University · GBKing's College London · GBUniversity of Warwick · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimer's disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways.

Indexed as

AdultAlzheimer DiseaseAmyloidAmyloid beta-PeptidesCell DifferentiationCell Line, TumorDimerizationDown-RegulationFluorescence Resonance Energy TransferHEK293 CellsHippocampusHumansMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Orexin ReceptorsPeptide FragmentsAmyloidAmyloid beta-Peptidesamyloid beta-protein (1-42)Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Orexin ReceptorsPeptide FragmentsQRFPR protein, humanReceptors, G-Protein-Coupledtau ProteinsTretinoinZinc Sulfate

Identifiers

PMID26223541
PMCPMC4519789
OpenAlexW1841221756

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.