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For: Davies J, Chen J, Pink R, Carter D, Saunders N, Sotiriadis G, Bai B, Pan Y, Howlett D, Payne A, Randeva H, Karteris E. Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103. Sci Rep 2015;5:12584. [PMID: 26223541 PMCID: PMC4519789 DOI: 10.1038/srep12584] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 05/29/2015] [Indexed: 12/22/2022] Open

For:	Davies J, Chen J, Pink R, Carter D, Saunders N, Sotiriadis G, Bai B, Pan Y, Howlett D, Payne A, Randeva H, Karteris E. Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103. Sci Rep 2015;5:12584. [PMID: 26223541 PMCID: PMC4519789 DOI: 10.1038/srep12584] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 05/29/2015] [Indexed: 12/22/2022] Open

Number

Cited by Other Article(s)

Zhuang C, Yan H, Lu J, Zhou Y, Liu Y, Shi G, Li Y. Compensatory enhancement of orexinergic system functionality induced by amyloid-β protein: a neuroprotective response in Alzheimer's disease. Front Physiol 2025;16:1529981. [PMID: 40196718 PMCID: PMC11973307 DOI: 10.3389/fphys.2025.1529981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open

Kourosh-Arami M, Ramezani M, Komaki A. The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection. J Physiol Sci 2025;75:100004. [PMID: 39823966 PMCID: PMC11979663 DOI: 10.1016/j.jphyss.2024.100004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/17/2024] [Accepted: 12/30/2024] [Indexed: 01/20/2025]

Kim SG, Keum M, Choe YM, Suh GH, Lee BC, Kim HS, Lee JH, Hwang J, Yi D, Kim JW. Selenium and Episodic Memory: The Moderating Role of Apolipoprotein E ε4. Nutrients 2025;17:595. [PMID: 39940451 PMCID: PMC11819958 DOI: 10.3390/nu17030595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/01/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open

Affiliation(s)

Shin Gyeom Kim Department of Neuropsychiatry, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea;
Musung Keum Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong 18450, Gyeonggi, Republic of Korea; (M.K.); (Y.M.C.); (G.-H.S.)
Young Min Choe Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong 18450, Gyeonggi, Republic of Korea; (M.K.); (Y.M.C.); (G.-H.S.) Department of Psychiatry, Hallym University College of Medicine, Chuncheon 24252, Gangwon, Republic of Korea;
Guk-Hee Suh Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong 18450, Gyeonggi, Republic of Korea; (M.K.); (Y.M.C.); (G.-H.S.) Department of Psychiatry, Hallym University College of Medicine, Chuncheon 24252, Gangwon, Republic of Korea;
Boung Chul Lee Department of Psychiatry, Hallym University College of Medicine, Chuncheon 24252, Gangwon, Republic of Korea; Department of Neuropsychiatry, Hallym University Hangang Sacred Heart Hospital, Seoul 07247, Republic of Korea
Hyun Soo Kim Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong 18450, Gyeonggi, Republic of Korea;
Jun Hyung Lee Department of Laboratory Medicine, Green Cross Laboratories (GC Labs), Yongin 16924, Gyeonggi, Republic of Korea;
Jaeuk Hwang Department of Psychiatry, Soonchunhyang University Hospital Seoul, Seoul 04401, Republic of Korea;
Dahyun Yi Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul 03080, Republic of Korea;
Jee Wook Kim Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong 18450, Gyeonggi, Republic of Korea; (M.K.); (Y.M.C.); (G.-H.S.) Department of Psychiatry, Hallym University College of Medicine, Chuncheon 24252, Gangwon, Republic of Korea;

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Chen YM, Huang J, Fan H, Li WY, Shi TS, Zhao J, Wang CN, Chen WJ, Zhu BL, Qian JJ, Guan W, Jiang B. QRFP and GPR103 in the paraventricular nucleus play a role in chronic stress-induced depressive-like symptomatology by enhancing the hypothalamic-pituitary-adrenal axis. Neuropharmacology 2025;262:110198. [PMID: 39442911 DOI: 10.1016/j.neuropharm.2024.110198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 10/04/2024] [Accepted: 10/19/2024] [Indexed: 10/25/2024]

Jászberényi M, Thurzó B, Jayakumar AR, Schally AV. The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease. Int J Mol Sci 2024;25:13086. [PMID: 39684795 DOI: 10.3390/ijms252313086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open

Joshi A, Giorgi FM, Sanna PP. Transcriptional Patterns in Stages of Alzheimer's Disease Are Cell-Type-Specific and Partially Converge with the Effects of Alcohol Use Disorder in Humans. eNeuro 2024;11:ENEURO.0118-24.2024. [PMID: 39299805 PMCID: PMC11485264 DOI: 10.1523/eneuro.0118-24.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 07/24/2024] [Accepted: 09/04/2024] [Indexed: 09/22/2024] Open

Lozano-Tovar S, Nuccetelli M, Placidi F, Izzi F, Sancesario G, Bernardini S, Biagio Mercuri N, Liguori C. CSF dynamics of orexin and β-amyloid₄₂ levels in narcolepsy and Alzheimer's disease patients: a controlled study. Neurosci Lett 2024;837:137914. [PMID: 39032802 DOI: 10.1016/j.neulet.2024.137914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 06/12/2024] [Accepted: 07/17/2024] [Indexed: 07/23/2024]

Abstract

β-amyloid42 (Aβ42) in Alzheimer's disease (AD) and orexin in narcolepsy are considered crucial biomarkers for diagnosis and therapeutic targets. Recently, orexin and Aβ cerebral dynamics have been studied in both pathologies, but how they interact with each other remains further to be known. In this study, we investigated the reliability of using the correlation between orexin-A and Aβ42 CSF levels as a candidate marker to explain the chain of events leading to narcolepsy or AD pathology. In order to test the correlation between these biomarkers, patients diagnosed with AD (n = 76), narcolepsy type 1 (NT1, n = 17), narcolepsy type 2 (NT2, n = 23) and healthy subjects (n = 91) were examined. Patients and healthy subjects underwent lumbar puncture between 8:00 and 10:00 am at the Neurology Unit of the University Hospital of Rome "Tor Vergata". CSF levels of Aβ42, total-tau, phosphorylated-tau, and orexin-A were assessed. The results showed that CSF levels of Aβ42 were significantly lower (p < 0.001) in AD (332.28 ± 237.36 pg/mL) compared to NT1 (569.88 ± 187.00 pg/mL), NT2 (691.00 ± 292.63 pg/mL) and healthy subjects (943.68 ± 198.12 pg/mL). CSF orexin-A levels were statistically different (p < 0.001) between AD (148.01 ± 29.49 pg/mL), NT1 (45.94 ± 13.63 pg/mL), NT2 (104.92 ± 25.55 pg/mL) and healthy subjects (145.18 ± 27.01 pg/mL). Moderate-severe AD patients (mini mental state examination < 21) showed the highest CSF orexin-A levels, whereas NT1 patients showed the lowest CSF orexin-A levels. Correlation between CSF levels of Aβ42 and orexin-A was found only in healthy subjects (r = 0.26; p = 0.01), and not in narcolepsy or AD patients. This lack of correlation in both diseases may be explained by the pathology itself since the correlation between these two biomarkers is evident only in the healthy subjects. This study adds to the present literature by further documenting the interplay between orexinergic neurotransmission and cerebral Aβ dynamics, possibly sustained by sleep.

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Kovács A, Szabó E, László K, Kertes E, Zagorácz O, Mintál K, Tóth A, Gálosi R, Berta B, Lénárd L, Hormay E, László B, Zelena D, Tóth ZE. Brain RFamide Neuropeptides in Stress-Related Psychopathologies. Cells 2024;13:1097. [PMID: 38994950 PMCID: PMC11240450 DOI: 10.3390/cells13131097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/21/2024] [Accepted: 06/22/2024] [Indexed: 07/13/2024] Open

Affiliation(s)

Anita Kovács Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Evelin Szabó Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Kristóf László Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Erika Kertes Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Olga Zagorácz Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Kitti Mintál Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Attila Tóth Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Rita Gálosi Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Bea Berta Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
László Lénárd Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Edina Hormay Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Bettina László Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Dóra Zelena Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary; (A.K.); (E.S.); (K.L.); (E.K.); (O.Z.); (K.M.); (A.T.); (R.G.); (B.B.); (L.L.); (E.H.); (B.L.)
Zsuzsanna E. Tóth Department of Anatomy, Histology and Embryology, Semmelweis University, H1094 Budapest, Hungary

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Satpati A, Pereira FL, Soloviev AV, Mladinov M, Larsen E, Hua SL, Tu CL, Leite REP, Suemoto CK, Rodriguez RD, Paes VR, Walsh C, Spina S, Seeley WW, Pasqualucci CA, Filho WJ, Chang W, Neylan TC, Grinberg LT. The wake- and sleep-modulating neurons of the lateral hypothalamic area demonstrate a differential pattern of degeneration in Alzheimers disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.06.583765. [PMID: 38559184 PMCID: PMC10979907 DOI: 10.1101/2024.03.06.583765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]

Abstract

BACKGROUND

Sleep-wake dysfunction is an early and common event in Alzheimer's disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic neurons (OrxN) and sleep-promoting melanin-concentrating hormone or MCHergic neurons (MCHN). These neurons share close anatomical proximity with functional reciprocity. This study investigated LHA OrxN and MCHN loss patterns in AD individuals. Understanding the degeneration pattern of these neurons will be instrumental in designing potential therapeutics to slow down the disease progression and remediate the sleep-wake dysfunction in AD.

METHODS

Postmortem human brain tissue from donors with AD (across progressive stages) and controls were examined using unbiased stereology. Formalin-fixed, celloidin-embedded hypothalamic sections were stained with Orx-A/MCH, p-tau (CP13), and counterstained with gallocyanin. Orx or MCH-positive neurons with or without CP13 inclusions and gallocyanin-stained neurons were considered for stereology counting. Additionally, we extracted RNA from the LHA using conventional techniques. We used customized Neuropathology and Glia nCounter (Nanostring) panels to study gene expression. Wald statistical test was used to compare the groups, and the genes were considered differentially expressed when the p-value was <.05.

RESULTS

We observed a progressive decline in OrxN alongside a relative preservation of MCHN. OrxN decreased by 58% (p=0.03) by Braak stages (BB) 1-2 and further declined to 81% (p=0.03) by BB 5-6. Conversely, MCHN demonstrated a non-statistical significant decline (27%, p=0.1088) by BB 6. We observed a progressive increase in differentially expressed genes (DEGs), starting with glial profile changes in BB2. While OrxN loss was observed, Orx-related genes showed upregulation in BB 3-4 compared to BB 0-1. GO and KEGG terms related to neuroinflammatory pathways were mainly enriched.

CONCLUSIONS

To date, OrxN loss in the LHA represents the first neuronal population to die preceding the loss of LC neurons. Conversely, MCHN shows resilience to AD p-tau accumulation across Braak stages. The initial loss of OrxN correlates with specific neuroinflammation, glial profile changes, and an overexpression of HCRT, possibly due to hyperexcitation following compensation mechanisms. Interventions preventing OrxN loss and inhibiting p-tau accumulation in the LHA could prevent neuronal loss in AD and, perhaps, the progression of the disease.

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Devère M, Takhlidjt S, Prévost G, Chartrel N, Leprince J, Picot M. The 26RFa (QRFP)/GPR103 Neuropeptidergic System: A Key Regulator of Energy and Glucose Metabolism. Neuroendocrinology 2024;115:111-127. [PMID: 38599200 DOI: 10.1159/000538629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 03/28/2024] [Indexed: 04/12/2024]

Abstract

BACKGROUND

Obesity and type 2 diabetes are strongly associated pathologies, currently considered as a worldwide epidemic problem. Understanding the mechanisms that drive the development of these diseases would enable to develop new therapeutic strategies for their prevention and treatment. Particularly, the role of the brain in energy and glucose homeostasis has been studied for 2 decades. In specific, the hypothalamus contains well-identified neural networks that regulate appetite and potentially also glucose homeostasis. A new concept has thus emerged, suggesting that obesity and diabetes could be due to a dysfunction of the same, still poorly understood, neural networks.

SUMMARY

The neuropeptide 26RFa (also termed QRFP) belongs to the family of RFamide regulatory peptides and has been identified as the endogenous ligand of the human G protein-coupled receptor GPR103 (QRFPR). The primary structure of 26RFa is strongly conserved during vertebrate evolution, suggesting its crucial roles in the control of vital functions. Indeed, the 26RFa/GPR103 peptidergic system is reported to be involved in the control of various neuroendocrine functions, notably the control of energy metabolism in which it plays an important role, both centrally and peripherally, since 26RFa regulates feeding behavior, thermogenesis and lipogenesis. Moreover, 26RFa is reported to control glucose homeostasis both peripherally, where it acts as an incretin, and centrally, where the 26RFa/GPR103 system relays insulin signaling in the brain to control glucose metabolism.

KEY MESSAGES

This review gives a comprehensive overview of the role of the 26RFa/GPR103 system as a key player in the control of energy and glucose metabolism. In a pathophysiological context, this neuropeptidergic system represents a prime therapeutic target whose mechanisms are highly relevant to decipher.

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Farajzadeh-Dehkordi M, Mafakher L, Harifi A, Haghdoost-Yazdi H, Piri H, Rahmani B. Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis. Sci Rep 2024;14:833. [PMID: 38191899 PMCID: PMC10774445 DOI: 10.1038/s41598-023-49809-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 12/12/2023] [Indexed: 01/10/2024] Open

Tang M, Wu L, Shen Z, Chen J, Yang Y, Zhang M, Zhao P, Jiang G. Association between Sleep and Alzheimer's Disease: A Bibliometric Analysis from 2003 to 2022. Neuroepidemiology 2023;57:377-390. [PMID: 37699365 DOI: 10.1159/000533700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 07/26/2023] [Indexed: 09/14/2023] Open

Edwards GA, Wood CA, Nguyen Q, Kim PJ, Gomez-Gutierrez R, Park KW, Zurhellen C, Al-Ramahi I, Jankowsky JL. TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.03.23.533978. [PMID: 36993574 PMCID: PMC10055407 DOI: 10.1101/2023.03.23.533978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]

Lozano-Tovar S, Rodríguez-Agudelo Y, Dávila-Ortiz de Montellano DJ, Pérez-Aldana BE, Ortega-Vázquez A, Monroy-Jaramillo N. Relationship between APOE, PER2, PER3 and OX2R Genetic Variants and Neuropsychiatric Symptoms in Patients with Alzheimer's Disease. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023;20:4412. [PMID: 36901420 PMCID: PMC10001852 DOI: 10.3390/ijerph20054412] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/20/2023] [Accepted: 02/27/2023] [Indexed: 06/18/2023]

Ball HL, Said H, Chapman K, Fu R, Xiong Y, Burk JA, Rosenbaum D, Veneziano R, Cotten ML. Orexin A, an amphipathic α-helical neuropeptide involved in pleiotropic functions in the nervous and immune systems: Synthetic approach and biophysical studies of the membrane-bound state. Biophys Chem 2023;297:107007. [PMID: 37037119 DOI: 10.1016/j.bpc.2023.107007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/11/2023] [Accepted: 03/12/2023] [Indexed: 03/16/2023]

Abstract

This research reports on the membrane interactions of orexin A (OXA), an α-helical and amphipathic neuropeptide that contains 33 residues and two disulfide bonds in the N-terminal region. OXA, which activates the orexins 1 and 2 receptors in neural and immune cell membranes, has essential pleiotropic physiological effects, including at the levels of arousal, sleep/wakefulness, energy balance, neuroprotection, lipid signaling, the inflammatory response, and pain. As a result, the orexin system has become a prominent target to treat diseases such as sleep disorders, drug addiction, and inflammation. While the high-resolution structure of OXA has been investigated in water and bound to micelles, there is a lack of information about its conformation bound to phospholipid membranes and its receptors. NMR is a powerful method to investigate peptide structures in a membrane environment. To facilitate the NMR structural studies of OXA exposed to membranes, we present a novel synthetic scheme, leading to the production of isotopically-labeled material at high purity. A receptor activation assay shows that the ¹⁵N-labeled peptide is biologically active. Biophysical studies are performed using surface plasmon resonance, circular dichroism, and NMR to investigate the interactions of OXA with phospholipid bilayers. The results demonstrate a strong interaction between the peptide and phospholipids, an increase in α-helical content upon membrane binding, and an in-plane orientation of the C-terminal region critical to function. This new knowledge about structure-activity relationships in OXA could inspire the design of novel therapeutics that leverage the anti-inflammatory and neuro-protective functions of OXA, and therefore could help address neuroinflammation, a major issue associated with neurological disorders such as Alzheimer's disease.

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Haddad M, Khazali H, Janahmadi M, Ghanbarian H. Inhibition of the retinal orexin receptors affects the hypothalamic-pituitary-gonadal axis through retinal pituitary adenylate cyclase activating polypeptide (PACAP) in male Wistar rats. Gen Comp Endocrinol 2023;337:114242. [PMID: 36801394 DOI: 10.1016/j.ygcen.2023.114242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/08/2023] [Accepted: 02/15/2023] [Indexed: 02/19/2023]

Ishioh M, Nozu T, Miyagishi S, Igarashi S, Funayama T, Ohhira M, Okumura T. Activation of basal forebrain cholinergic neurons improves colonic hyperpermeability through the vagus nerve and adenosine A2B receptors in rats. Biochem Pharmacol 2022;206:115331. [PMID: 36330948 DOI: 10.1016/j.bcp.2022.115331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/20/2022] [Accepted: 10/24/2022] [Indexed: 12/14/2022]

Cook C, Nunn N, Worth AA, Bechtold DA, Suter T, Gackeheimer S, Foltz L, Emmerson PJ, Statnick MA, Luckman SM. The hypothalamic RFamide, QRFP, increases feeding and locomotor activity: The role of Gpr103 and orexin receptors. PLoS One 2022;17:e0275604. [PMID: 36251705 PMCID: PMC9576062 DOI: 10.1371/journal.pone.0275604] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 09/20/2022] [Indexed: 11/08/2022] Open

Huang L, Kang J, Chen G, Ye W, Meng X, Du Q, Feng Z. Low-intensity focused ultrasound attenuates early traumatic brain injury by OX-A/NF-κB/NLRP3 signaling pathway. Aging (Albany NY) 2022;14:7455-7469. [PMID: 36126193 PMCID: PMC9550253 DOI: 10.18632/aging.204290] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 08/03/2022] [Indexed: 11/25/2022]

Luo Y, Shan L, Xu L, Patnala S, Kanfer I, Li J, Yu P, Jun X. A network pharmacology-based approach to explore the therapeutic potential of Sceletium tortuosum in the treatment of neurodegenerative disorders. PLoS One 2022;17:e0273583. [PMID: 36006974 PMCID: PMC9409587 DOI: 10.1371/journal.pone.0273583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 08/10/2022] [Indexed: 11/24/2022] Open

Sun YY, Wang Z, Zhou HY, Huang HC. Sleep-Wake Disorders in Alzheimer's Disease: A Review. ACS Chem Neurosci 2022;13:1467-1478. [PMID: 35507669 DOI: 10.1021/acschemneuro.2c00097] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open

Elahdadi Salmani M, Sarfi M, Goudarzi I. Hippocampal orexin receptors: Localization and function. VITAMINS AND HORMONES 2022;118:393-421. [PMID: 35180935 DOI: 10.1016/bs.vh.2021.12.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]

Patel SK, Singh SK. Pyroglutamylated RFamide peptide (QRFP): Role in early testicular development in relation to Sertoli cell maturation in prepubertal mice. Neuropeptides 2022;91:102215. [PMID: 34883413 DOI: 10.1016/j.npep.2021.102215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 11/30/2021] [Accepted: 11/30/2021] [Indexed: 11/18/2022]

Kondo T, Hara N, Koyama S, Yada Y, Tsukita K, Nagahashi A, Ikeuchi T, Ishii K, Asada T, Arai T, Yamada R, Inoue H. Dissection of the polygenic architecture of neuronal Aβ production using a large sample of individual iPSC lines derived from Alzheimer's disease patients. NATURE AGING 2022;2:125-139. [PMID: 37117761 DOI: 10.1038/s43587-021-00158-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 11/23/2021] [Indexed: 04/30/2023]

Affiliation(s)

Takayuki Kondo Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center (BRC), Kyoto, Japan
Norikazu Hara Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
Satoshi Koyama Unit of Statistical Genetics, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Yuichiro Yada Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center (BRC), Kyoto, Japan
Kayoko Tsukita Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center (BRC), Kyoto, Japan
Ayako Nagahashi Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Takeshi Ikeuchi Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
Kenji Ishii Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Takashi Asada Department of Psychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Tetsuaki Arai Department of Psychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Ryo Yamada Unit of Statistical Genetics, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Haruhisa Inoue Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center (BRC), Kyoto, Japan. Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital, Kyoto, Japan.

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Madaan P, Behl T, Sehgal A, Singh S, Sharma N, Yadav S, Kaur S, Bhatia S, Al-Harrasi A, Abdellatif AAH, Ashraf GM, Abdel-Daim MM, Dailah HG, Anwer MK, Bungau S. Exploring the Therapeutic Potential of Targeting Purinergic and Orexinergic Receptors in Alcoholic Neuropathy. Neurotox Res 2022;40:646-669. [DOI: 10.1007/s12640-022-00477-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 01/13/2022] [Accepted: 01/19/2022] [Indexed: 12/11/2022]

Couvineau A, Voisin T, Nicole P, Gratio V, Blais A. Orexins: A promising target to digestive cancers, inflammation, obesity and metabolism dysfunctions. World J Gastroenterol 2021;27:7582-7596. [PMID: 34908800 PMCID: PMC8641057 DOI: 10.3748/wjg.v27.i44.7582] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/22/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open

Gao F, Liu T, Tuo M, Chi S. The role of orexin in Alzheimer disease: From sleep-wake disturbance to therapeutic target. Neurosci Lett 2021;765:136247. [PMID: 34530113 DOI: 10.1016/j.neulet.2021.136247] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 08/01/2021] [Accepted: 09/09/2021] [Indexed: 10/20/2022]

Wang W, Tian Y, Shi X, Ma Q, Xu Y, Yang G, Yi W, Shi Y, Zhou N. N-glycosylation of the human neuropeptide QRFP receptor (QRFPR) is essential for ligand binding and receptor activation. J Neurochem 2021;158:138-152. [PMID: 33655503 DOI: 10.1111/jnc.15337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 11/29/2022]

Zhan D, Perrer DA, Decker AM, Langston TL, Mavanji V, Harris DL, Kotz CM, Zhang Y. Discovery of Arylsulfonamides as Dual Orexin Receptor Agonists. J Med Chem 2021;64:8806-8825. [PMID: 34101446 PMCID: PMC8994207 DOI: 10.1021/acs.jmedchem.1c00841] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]

Erichsen JM, Calva CB, Reagan LP, Fadel JR. Intranasal insulin and orexins to treat age-related cognitive decline. Physiol Behav 2021;234:113370. [PMID: 33621561 PMCID: PMC8053680 DOI: 10.1016/j.physbeh.2021.113370] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023]

Siddappaji KK, Gopal S. Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches. AIMS Neurosci 2021;8:357-389. [PMID: 34183987 PMCID: PMC8222772 DOI: 10.3934/neuroscience.2021020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 03/16/2021] [Indexed: 11/18/2022] Open

Keenan RJ, Oberrauch S, Bron R, Nowell CJ, Challis LM, Hoyer D, Jacobson LH. Decreased Orexin Receptor 1 mRNA Expression in the Locus Coeruleus in Both Tau Transgenic rTg4510 and Tau Knockout Mice and Accompanying Ascending Arousal System Tau Invasion in rTg4510. J Alzheimers Dis 2021;79:693-708. [PMID: 33361602 DOI: 10.3233/jad-201177] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]

Seigneur E, de Lecea L. Hypocretin (Orexin) Replacement Therapies. MEDICINE IN DRUG DISCOVERY 2020;8:100070. [PMID: 38738170 PMCID: PMC11086741 DOI: 10.1016/j.medidd.2020.100070] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open

Yaeger JD, Krupp KT, Gale JJ, Summers CH. Counterbalanced microcircuits for Orx1 and Orx2 regulation of stress reactivity. MEDICINE IN DRUG DISCOVERY 2020. [DOI: 10.1016/j.medidd.2020.100059] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open

Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway. Cell Signal 2020;79:109839. [PMID: 33212156 DOI: 10.1016/j.cellsig.2020.109839] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/13/2020] [Accepted: 11/13/2020] [Indexed: 02/06/2023]

Wang W, Jiang C, Xu Y, Ma Q, Yang J, Shi Y, Zhou N. Functional characterization of neuropeptide 26RFa receptors GPR103A and GPR103B in zebrafish, Danio rerio. Cell Signal 2020;73:109677. [PMID: 32470519 DOI: 10.1016/j.cellsig.2020.109677] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 05/10/2020] [Accepted: 05/23/2020] [Indexed: 11/25/2022]

Sharma A, Lee S, Kim H, Yoon H, Ha S, Kang SU. Molecular Crosstalk Between Circadian Rhythmicity and the Development of Neurodegenerative Disorders. Front Neurosci 2020;14:844. [PMID: 32848588 PMCID: PMC7424028 DOI: 10.3389/fnins.2020.00844] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/20/2020] [Indexed: 12/17/2022] Open

Orexins role in neurodegenerative diseases: From pathogenesis to treatment. Pharmacol Biochem Behav 2020;194:172929. [PMID: 32315694 DOI: 10.1016/j.pbb.2020.172929] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 04/07/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]

Calva CB, Fadel JR. Intranasal administration of orexin peptides: Mechanisms and therapeutic potential for age-related cognitive dysfunction. Brain Res 2020;1731:145921. [PMID: 30148983 PMCID: PMC6387866 DOI: 10.1016/j.brainres.2018.08.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 08/03/2018] [Accepted: 08/23/2018] [Indexed: 12/11/2022]

Pallais JP, Kotz CM, Stanojlovic M. Orexin/hypocretinin in multiple sclerosis and experimental autoimmune encephalomyelitis. Neural Regen Res 2020;15:1039-1040. [PMID: 31823881 PMCID: PMC7034266 DOI: 10.4103/1673-5374.270310] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Zagorácz O, Ollmann T, Péczely L, László K, Kovács A, Berta B, Kállai V, Kertes E, Lénárd L. QRFP administration into the medial hypothalamic nuclei improves memory in rats. Brain Res 2019;1727:146563. [PMID: 31765630 DOI: 10.1016/j.brainres.2019.146563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 10/31/2019] [Accepted: 11/19/2019] [Indexed: 10/25/2022]

Couvineau A, Voisin T, Nicole P, Gratio V, Abad C, Tan YV. Orexins as Novel Therapeutic Targets in Inflammatory and Neurodegenerative Diseases. Front Endocrinol (Lausanne) 2019;10:709. [PMID: 31695678 PMCID: PMC6817618 DOI: 10.3389/fendo.2019.00709] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/02/2019] [Indexed: 02/05/2023] Open

Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons. Proc Natl Acad Sci U S A 2019;116:17061-17070. [PMID: 31375626 PMCID: PMC6708384 DOI: 10.1073/pnas.1902148116] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open

Kumar J, Murugaiah V, Sotiriadis G, Kaur A, Jeyaneethi J, Sturniolo I, Alhamlan FS, Chatterjee J, Hall M, Kishore U, Karteris E. Surfactant Protein D as a Potential Biomarker and Therapeutic Target in Ovarian Cancer. Front Oncol 2019;9:542. [PMID: 31338320 PMCID: PMC6629871 DOI: 10.3389/fonc.2019.00542] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 06/04/2019] [Indexed: 12/11/2022] Open

Abstract

Surfactant protein D (SP-D) is an important innate immune molecule that is involved in clearing pathogens and regulating inflammation at pulmonary as well as extra-pulmonary sites. Recent studies have established the role of SP-D as an innate immune surveillance molecule against lung and pancreatic cancer, but little is known about its involvement in signaling pathways it can potentially activate in ovarian cancer. We focused our study on ovarian cancer by performing bioinformatics analysis (Oncomine) of datasets and survival analysis (Kaplan-Meier plotter), followed by immunohistochemistry using ovarian cancer tissue microarrays. SP-D mRNA was found to be expressed widely in different types of ovarian cancer irrespective of stage or grade. These in silico data were further validated by immunohistochemistry of clinical tissues. High transcriptional levels of SP-D were associated with unfavorable prognosis (overall and progression-free survival). We also detected SP-D protein in Circulating Tumor Cells of three ovarian cancer patients, suggesting that SP-D can also be used as a potential biomarker. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis in pancreatic cancer cells via Fas-mediated pathway. In this study, we report that treatment of SKOV3 cells (an ovarian cancer cell line) with rfhSP-D led to a decrease in cell motility and cell proliferation. This was followed by an inhibition of the mTOR pathway activity, increase in caspase 3 cleavage, and induction of pro-apoptotic genes Fas and TNF-α. These data, suggesting a likely protective role of rfhSP-D against ovarian cancer, together with the observation that the ovarian cancer microenvironment overexperesses SP-D leading to poor prognosis, seems to suggest that the tumor microenvironment components manipulate the protective effect of SP-D in vivo.

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Niknia S, Kaeidi A, Hajizadeh MR, Mirzaei MR, Khoshdel A, Hajializadeh Z, Fahmidehkar MA, Mahmoodi M. Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy. Neuropeptides 2019;73:34-40. [PMID: 30447858 DOI: 10.1016/j.npep.2018.11.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 11/06/2018] [Accepted: 11/06/2018] [Indexed: 01/19/2023]

Affiliation(s)

Seddigheh Niknia Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Ayat Kaeidi Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Mohammad Reza Hajizadeh Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Mohammad Reza Mirzaei Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Alireza Khoshdel Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Zahra Hajializadeh Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Mohammad Ali Fahmidehkar Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Laboratory Science, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
Mehdi Mahmoodi Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Clinical Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

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Chen XY, Du YF, Chen L. Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease. Front Mol Neurosci 2019;11:493. [PMID: 30687008 PMCID: PMC6336706 DOI: 10.3389/fnmol.2018.00493] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Accepted: 12/21/2018] [Indexed: 01/03/2023] Open

Appetite, Metabolism and Hormonal Regulation in Normal Ageing and Dementia. Diseases 2018;6:diseases6030066. [PMID: 30036957 PMCID: PMC6164971 DOI: 10.3390/diseases6030066] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Revised: 07/17/2018] [Accepted: 07/19/2018] [Indexed: 12/12/2022] Open

Xue Q, Bai B, Ji B, Chen X, Wang C, Wang P, Yang C, Zhang R, Jiang Y, Pan Y, Cheng B, Chen J. Ghrelin Through GHSR1a and OX1R Heterodimers Reveals a Gαs-cAMP-cAMP Response Element Binding Protein Signaling Pathway in Vitro. Front Mol Neurosci 2018;11:245. [PMID: 30065627 PMCID: PMC6056640 DOI: 10.3389/fnmol.2018.00245] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 06/25/2018] [Indexed: 01/19/2023] Open

Sil’kis IG. A Neurochemical Approach to the Search for Drugs for the Treatment of Symptoms of Alzheimer’s Disease. NEUROCHEM J+ 2018. [DOI: 10.1134/s1819712418010130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]

Peineau S, Rabiant K, Pierrefiche O, Potier B. Synaptic plasticity modulation by circulating peptides and metaplasticity: Involvement in Alzheimer's disease. Pharmacol Res 2018;130:385-401. [PMID: 29425728 DOI: 10.1016/j.phrs.2018.01.018] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 01/23/2018] [Accepted: 01/26/2018] [Indexed: 10/18/2022]