NMDARs in neurological diseases: a potential therapeutic target

被引:57
作者
Gonzalez, Janneth [1 ]
Camilo Jurado-Coronel, Juan [1 ]
Fidel Avila, Marcos [1 ]
Sabogal, Angelica [1 ]
Capani, Francisco [2 ]
Barreto, George E. [1 ]
机构
[1] Pontificia Univ javeriana, Fac Ciencias, Dept Nutr & Bioquim, Bogota, DC, Colombia
[2] UBA, CONICET, Inst Invest Cardiol Prof Dr Alberto C Taquini INI, Lab Citoarquitectura & Plasticidad Neuronal, Buenos Aires, DF, Argentina
关键词
NMDARs; neurological diseases; antagonist; antioxidants; Alzheimer's disease; Parkinson's disease; D-ASPARTATE RECEPTOR; IONOTROPIC GLUTAMATE RECEPTORS; LONG-TERM POTENTIATION; EXCITATORY AMINO-ACID; ALZHEIMERS-DISEASE; SUBUNIT EXPRESSION; IN-VITRO; ANTIPARKINSONIAN ACTIONS; 6-HYDROXYDOPAMINE MODEL; NATURAL ANTIOXIDANTS;
D O I
10.3109/00207454.2014.940941
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
N-methyl-D-aspartate ionotropic glutamate receptor (NMDARs) is a ligand-gated ion channel that plays a critical role in excitatory neurotransmission, brain development, synaptic plasticity associated with memory formation, central sensitization during persistent pain, excitotoxicity and neurodegenerative diseases in the central nervous system (CNS). Within iGluRs, NMDA receptors have been the most actively investigated for their role in neurological diseases, especially neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases. It has been demonstrated that excessive activation of NMDA receptors (NMDARs) plays a key role in mediating some aspects of synaptic dysfunction in several CNS disorders, so extensive research has been directed on the discovery of compounds that are able to reduce NMDARs activity. This review discusses the role of NMDARs on neurological pathologies and the possible therapeutic use of agents that target this receptor. Additionally, we delve into the role of NMDARs in Alzheimer's and Parkinson's diseases and the receptor antagonists that have been tested on in vivo models of these pathologies. Finally, we put into consideration the importance of antioxidants to counteract oxidative capacity of the signaling cascade in which NMDARs are involved.
引用
收藏
页码:315 / 327
页数:13
相关论文
共 148 条
  • [1] Adamec RE, 1999, PHYSIOL BEHAV, V65, P723
  • [2] Disease-modifying drugs and Parkinson's disease
    Allain, Herve
    Bentue-Ferrer, Daniele
    Akwa, Yvette
    [J]. PROGRESS IN NEUROBIOLOGY, 2008, 84 (01) : 25 - 39
  • [3] Group III and subtype 4 metabotropic glutamate receptor agonists: Discovery and pathophysiological applications in Parkinson's disease
    Amalric, M.
    Lopez, S.
    Goudet, C.
    Fisone, G.
    Battaglia, G.
    Nicoletti, F.
    Pin, J. -P.
    Acher, F. C.
    [J]. NEUROPHARMACOLOGY, 2013, 66 : 53 - 64
  • [4] Neuroprotective interaction effects of NMDA and AMPA receptor antagonists in an in vitro model of cerebral ischemia
    Arias, RL
    Tasse, JRP
    Bowlby, MR
    [J]. BRAIN RESEARCH, 1999, 816 (02) : 299 - 308
  • [5] Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease
    Armentero, MT
    Fancellu, R
    Nappi, G
    Bramanti, P
    Blandini, F
    [J]. NEUROBIOLOGY OF DISEASE, 2006, 22 (01) : 1 - 9
  • [6] Selective mGluR5 receptor antagonist or agonist provides neuroprotection in a rat model of focal cerebral ischemia
    Bao, WL
    Williams, AJ
    Faden, AI
    Tortella, FC
    [J]. BRAIN RESEARCH, 2001, 922 (02) : 173 - 179
  • [7] Similar anxiolytic-like effects following intra-amygdala infusions of benzodiazepine receptor agonist and antagonist: Evidence for the release of an endogenous benzodiazepine inverse agonist in mice exposed to elevated plus-maze test
    Barbalho, Cilene Aparecida
    Nunes-de-Souza, Ricardo L.
    Canto-de-Souza, Azair
    [J]. BRAIN RESEARCH, 2009, 1267 : 65 - 76
  • [8] Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
    Belforte, Juan E.
    Zsiros, Veronika
    Sklar, Elyse R.
    Jiang, Zhihong
    Yu, Gu
    Li, Yuqing
    Quinlan, Elizabeth M.
    Nakazawa, Kazu
    [J]. NATURE NEUROSCIENCE, 2010, 13 (01) : 76 - U240
  • [9] Antidepressant effects of ketamine in depressed patients
    Berman, RM
    Cappiello, A
    Anand, A
    Oren, DA
    Heninger, GR
    Charney, DS
    Krystal, JH
    [J]. BIOLOGICAL PSYCHIATRY, 2000, 47 (04) : 351 - 354
  • [10] Bespalov AY, 1999, J PHARMACOL EXP THER, V290, P20