{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:35:22Z","timestamp":1793367322607,"version":"4.5.0"},"reference-count":103,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Innovation","award":["PID2020-113430RB-I00"],"award-info":[{"award-number":["PID2020-113430RB-I00"]}]},{"name":"Spanish Ministry of Economy and Innovation","award":["2021 SGR 554 00304"],"award-info":[{"award-number":["2021 SGR 554 00304"]}]},{"name":"Regional Catalonian Government.","award":["PID2020-113430RB-I00"],"award-info":[{"award-number":["PID2020-113430RB-I00"]}]},{"name":"Regional Catalonian Government.","award":["2021 SGR 554 00304"],"award-info":[{"award-number":["2021 SGR 554 00304"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) remains a significant health challenge, with an increasing prevalence globally. Recent research has aimed to deepen the understanding of the disease pathophysiology and to find potential therapeutic interventions. In this regard, G protein-coupled receptors (GPCRs) have emerged as novel potential therapeutic targets to palliate the progression of neurodegenerative diseases such as AD. Orexin and cannabinoid receptors are GPCRs capable of forming heteromeric complexes with a relevant role in the development of this disease. On the one hand, the hyperactivation of the orexins system has been associated with sleep\u2013wake cycle disruption and A\u03b2 peptide accumulation. On the other hand, cannabinoid receptor overexpression takes place in a neuroinflammatory environment, favoring neuroprotective effects. Considering the high number of interactions between cannabinoid and orexin systems that have been described, regulation of this interplay emerges as a new focus of research. In fact, in microglial primary cultures of APPSw\/Ind mice model of AD there is an important increase in CB2R\u2013OX1R complex expression, while OX1R antagonism potentiates the neuroprotective effects of CB2R. Specifically, pretreatment with the OX1R antagonist has been shown to strongly potentiate CB2R signaling in the cAMP pathway. Furthermore, the blockade of OX1R can also abolish the detrimental effects of OX1R overactivation in AD. In this sense, CB2R\u2013OX1R becomes a new potential therapeutic target to combat AD.<\/jats:p>","DOI":"10.3390\/ijms25105378","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:35:55Z","timestamp":1715744155000},"page":"5378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cannabinoid and Orexigenic Systems Interplay as a New Focus of Research in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"given":"Joan Biel","family":"Rebassa","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos, 28029 Madrid, Spain"},{"name":"Institut de Neuroci\u00e8ncies UB, Campus Mundet, 08035 Barcelona, Spain"},{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Cap\u00f3","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos, 28029 Madrid, Spain"},{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Lillo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos, 28029 Madrid, Spain"},{"name":"Institut de Neuroci\u00e8ncies UB, Campus Mundet, 08035 Barcelona, Spain"},{"name":"Departament de Biochemistry and Molecular Biomedicine, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-0495","authenticated-orcid":false,"given":"Iu","family":"Ra\u00efch","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos, 28029 Madrid, Spain"},{"name":"Institut de Neuroci\u00e8ncies UB, Campus Mundet, 08035 Barcelona, Spain"},{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-2537","authenticated-orcid":false,"given":"Irene","family":"Reyes-Resina","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos, 28029 Madrid, Spain"},{"name":"Institut de Neuroci\u00e8ncies UB, Campus Mundet, 08035 Barcelona, Spain"},{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-0873","authenticated-orcid":false,"given":"Gemma","family":"Navarro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos, 28029 Madrid, Spain"},{"name":"Institut de Neuroci\u00e8ncies UB, Campus Mundet, 08035 Barcelona, Spain"},{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101998","DOI":"10.1016\/j.arr.2023.101998","article-title":"Under the Umbrella of Depression and Alzheimer\u2019s Disease Physiopathology: Can Cannabinoids Be a Dual-Pleiotropic Therapy?","volume":"90","author":"Fonseca","year":"2023","journal-title":"Ageing Res. 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