Articles producció científica> Bioquímica i Biotecnologia

Memantine for the treatment of dementia: A review on its current and future applications

  • Dades identificatives

    Identificador: imarina:5904153
    Autors:
    Folch JBusquets OEttcheto MSánchez-López ECastro-Torres RVerdaguer EGarcia MOlloquequi JCasadesús GBeas-Zarate CPelegri CVilaplana JAuladell CCamins A
    Resum:
    © 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.
  • Altres:

    Autor segons l'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
    Departament: Bioquímica i Biotecnologia
    Autor/s de la URV: Folch Lopez, Jaume
    Paraules clau: 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
    Resum: © 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.
    Àrees temàtiques: 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
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 13872877
    Adreça de correu electrònic de l'autor: jaume.folch@urv.cat
    Identificador de l'autor: 0000-0002-5051-8858
    Pàgina final: 1240
    Data d'alta del registre: 2024-09-07
    Volum de revista: 62
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170672
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Journal Of Alzheimers Disease. 62 (3): 1223-1240
    Referència de l'ítem segons les normes 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
    DOI de l'article: 10.3233/JAD-170672
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2018
    Pàgina inicial: 1223
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Clinical Psychology,Geriatrics and Gerontology,Medicine (Miscellaneous),Neuroscience (Miscellaneous),Neurosciences,Psychiatry and Mental Health
    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
    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
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