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http://hdl.handle.net/2445/173853
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DC Field | Value | Language |
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dc.contributor.author | Companys Alemany, Júlia | - |
dc.contributor.author | Turcu, Andreea L. | - |
dc.contributor.author | Bellver-Sanchis, Aina | - |
dc.contributor.author | Loza, María Isabel | - |
dc.contributor.author | Brea, José | - |
dc.contributor.author | Canudas Teixidó, Anna-Maria | - |
dc.contributor.author | Leiva Martínez, Rosana | - |
dc.contributor.author | Vázquez Cruz, Santiago | - |
dc.contributor.author | Pallàs i Llibería, Mercè, 1964- | - |
dc.contributor.author | Griñán Ferré, Christian | - |
dc.date.accessioned | 2021-02-11T11:12:51Z | - |
dc.date.available | 2021-02-11T11:12:51Z | - |
dc.date.issued | 2020-03-22 | - |
dc.identifier.issn | 1999-4923 | - |
dc.identifier.uri | http://hdl.handle.net/2445/173853 | - |
dc.description.abstract | Alzheimer's 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 e cacy 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. | - |
dc.format.extent | 17 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | MDPI | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3390/pharmaceutics12030284 | - |
dc.relation.ispartof | Pharmaceutics, 2020, vol. 12, num. 3 | - |
dc.relation.uri | https://doi.org/10.3390/pharmaceutics12030284 | - |
dc.rights | cc-by (c) Companys Alemany et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Malalties neurodegeneratives | - |
dc.subject.classification | Envelliment | - |
dc.subject.classification | Malaltia d'Alzheimer | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.subject.other | Aging | - |
dc.subject.other | Alzheimer's disease | - |
dc.title | A Novel NMDA Receptor Antagonist Protects against Cognitive Decline Presented by Senescent Mice | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 700734 | - |
dc.date.updated | 2021-02-11T11:12:51Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32235699 | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Institut de Neurociències (UBNeuro)) Articles publicats en revistes (Institut de Biomedicina (IBUB)) |
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700734.pdf | 4.13 MB | Adobe PDF | View/Open |
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