Author, as appears in the article.: Folch J; Busquets O; Ettcheto M; Sánchez-López E; Castro-Torres R; Verdaguer E; Garcia M; Olloquequi J; Casadesús G; Beas-Zarate C; Pelegri C; Vilaplana J; Auladell C; Camins A
Department: Bioquímica i Biotecnologia
URV's Author/s: Folch Lopez, Jaume
Keywords: Tau protein Neurodegeneration Memantine Extrasynaptic n-methyl-d-aspartate receptor Amyloid-protein Alzheimer's disease memantine extrasynaptic n-methyl-d-aspartate receptor amyloid ?-protein alzheimer’s disease
Abstract: © 2018 - IOS Press and the authors. All rights reserved. Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence in the brain of extracellular amyloid-βprotein (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. The N-Methyl-D-aspartate receptors (NMDAR), ionotropic glutamate receptor, are essential for processes like learning and memory. An excessive activation of NMDARs has been associated with neuronal loss. The discovery of extrasynaptic NMDARs provided a rational and physiological explanation between physiological and excitotoxic actions of glutamate. Memantine (MEM), an antagonist of extrasynaptic NMDAR, is currently used for the treatment of AD jointly with acetylcholinesterase inhibitors. It has been demonstrated that MEM preferentially prevents the excessive continuous extrasynaptic NMDAR disease activation and therefore prevents neuronal cell death induced by excitotoxicity without disrupting physiological synaptic activity. The problem is that MEM has shownno clear positive effects in clinical applications while, in preclinical stages, had very promising results. The data in preclinical studies suggests that MEM has a positive impact on improving AD brain neuropathology, as well as in preventing Aβ production, aggregation, or downstream neurotoxic consequences, in part through the blockade of extrasynaptic NMDAR. Thus, the focus of this review is primarily to discuss the efficacy of MEM in preclinical models of AD, consider possible combinations of this drug with others, and then evaluate possible reasons for its lack of efficacy in clinical trials. Finally, applications in other pathologies are also considered.
Thematic Areas: Sociología Saúde coletiva Psychiatry and mental health Psicología Odontología Neurosciences Neuroscience (miscellaneous) Neuroscience (all) Medicine (miscellaneous) Medicina ii Medicina i Matemática / probabilidade e estatística Interdisciplinar Geriatrics and gerontology General neuroscience General medicine Farmacia Engenharias iv Enfermagem Educação física Clinical psychology Ciencias sociales Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 13872877
Author's mail: jaume.folch@urv.cat
Author identifier: 0000-0002-5051-8858
Last page: 1240
Record's date: 2024-09-07
Journal volume: 62
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170672
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Journal Of Alzheimers Disease. 62 (3): 1223-1240
APA: Folch J; Busquets O; Ettcheto M; Sánchez-López E; Castro-Torres R; Verdaguer E; Garcia M; Olloquequi J; Casadesús G; Beas-Zarate C; Pelegri C; Vilapla (2018). Memantine for the treatment of dementia: A review on its current and future applications. Journal Of Alzheimers Disease, 62(3), 1223-1240. DOI: 10.3233/JAD-170672
Article's DOI: 10.3233/JAD-170672
Entity: Universitat Rovira i Virgili
Journal publication year: 2018
First page: 1223
Publication Type: Journal Publications