{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:03:08Z","timestamp":1790661788231,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,22]],"date-time":"2020-03-22T00:00:00Z","timestamp":1584835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2017-82771-R"],"award-info":[{"award-number":["SAF2017-82771-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2016-33307"],"award-info":[{"award-number":["SAF2016-33307"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2015-68749"],"award-info":[{"award-number":["SAF2015-68749"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2017-90913"],"award-info":[{"award-number":["SAF2017-90913"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","award":["2017 SGR 106"],"award-info":[{"award-number":["2017 SGR 106"]}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431C 2018\/21"],"award-info":[{"award-number":["ED431C 2018\/21"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia. Non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist memantine improved cognition and molecular alterations after preclinical treatment. Nevertheless, clinical results are discouraging. In vivo efficacy of the RL-208, a new NMDA receptor blocker described recently, with favourable pharmacokinetic properties was evaluated in Senescence accelerated mice prone 8 (SAMP8), a mice model of late-onset AD (LOAD). Oral administration of RL-208 improved cognitive performance assessed by using the three chamber test (TCT), novel object recognition test (NORT), and object location test (OLT). Consistent with behavioural results, RL-208 treated-mice groups significantly changed NMDAR2B phosphorylation state levels but not NMDAR2A. Calpain-1 and Caspase-3 activity was reduced, whereas B-cell lymphoma-2 (BCL-2) levels increased, indicating reduced apoptosis in RL-208 treated SAMP8. Superoxide Dismutase 1 (SOD1) and Glutathione Peroxidase 1 (GPX1), as well as a reduction of hydrogen peroxide (H2O2), was also determined in RL-208 mice. RL-208 treatment induced an increase in mature brain-derived neurotrophic factor (mBDNF), prevented Tropomyosin-related kinase B full-length (TrkB-FL) cleavage, increased protein levels of Synaptophysin (SYN) and Postsynaptic density protein 95 (PSD95). In whole, these results point out to an improvement in synaptic plasticity. Remarkably, RL-208 also decreased the protein levels of Cyclin-Dependent Kinase 5 (CDK5), as well as p25\/p35 ratio, indicating a reduction in kinase activity of CDK5\/p25 complex. Consequently, lower levels of hyperphosphorylated Tau (p-Tau) were found. In sum, these results demonstrate the neuroprotectant role of RL-208 through NMDAR blockade.<\/jats:p>","DOI":"10.3390\/pharmaceutics12030284","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T13:04:04Z","timestamp":1585055044000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["A Novel NMDA Receptor Antagonist Protects against Cognitive Decline Presented by Senescent Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-7700","authenticated-orcid":false,"given":"J\u00falia","family":"Companys-Alemany","sequence":"first","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea L.","family":"Turcu","sequence":"additional","affiliation":[{"name":"Laboratori de Qu\u00edmica Farmac\u00e8utica (Unitat Associada al CSIC), Department de Farmacologia, Toxicologia i Qu\u00edmica Terap\u00e8utica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina","family":"Bellver-Sanchis","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I","family":"Loza","sequence":"additional","affiliation":[{"name":"Innopharma Screening Platform, Biofarma Research Group, Centro de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas (CIMUS), Universidad de Santiago de Compostela, 15701 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Brea","sequence":"additional","affiliation":[{"name":"Innopharma Screening Platform, Biofarma Research Group, Centro de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas (CIMUS), Universidad de Santiago de Compostela, 15701 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Canudas","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosana","family":"Leiva","sequence":"additional","affiliation":[{"name":"Laboratori de Qu\u00edmica Farmac\u00e8utica (Unitat Associada al CSIC), Department de Farmacologia, Toxicologia i Qu\u00edmica Terap\u00e8utica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-6026","authenticated-orcid":false,"given":"Santiago","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratori de Qu\u00edmica Farmac\u00e8utica (Unitat Associada al CSIC), Department de Farmacologia, Toxicologia i Qu\u00edmica Terap\u00e8utica, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l\u2019Alimentaci\u00f3, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3095-4254","authenticated-orcid":false,"given":"Merc\u00e8","family":"Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-9130","authenticated-orcid":false,"given":"Christian","family":"Gri\u00f1\u00e1n-Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona (NeuroUB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6929732","DOI":"10.1155\/2018\/6929732","article-title":"Risk factors for the progression of mild cognitive impairment in different types of neurodegenerative disorders","volume":"2018","author":"Chen","year":"2018","journal-title":"Behav. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3233\/JAD-170664","article-title":"Understanding Epigenetics in the Neurodegeneration of Alzheimer\u2019s Disease: SAMP8 Mouse Model","volume":"62","author":"Corpas","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2018). 2018 Alzheimer\u2019s Disease Facts and Figures. 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