NMDARs in neurological diseases: a potential therapeutic target

被引:61
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
[71]  
2-F
[72]   Functional Roles of Synaptic and Extrasynaptic NMDA Receptors in Physiological and Pathological Neuronal Activities [J].
Li, Sheng-Tian ;
Ju, Jue-Gang .
CURRENT DRUG TARGETS, 2012, 13 (02) :207-221
[73]   Role of the NMDA receptor in cognitive deficits, anxiety and depressive-like behavior in juvenile and adult mice after neonatal dexamethasone exposure [J].
Li, Su-Xia ;
Fujita, Yuko ;
Zhang, Ji-Chun ;
Ren, Qian ;
Ishima, Tamaki ;
Wu, Jin ;
Hashimoto, Kenji .
NEUROBIOLOGY OF DISEASE, 2014, 62 :124-134
[74]   NMDA receptor activity regulates transcription of antioxidant pathways [J].
Lipton, Stuart A. .
NATURE NEUROSCIENCE, 2008, 11 (04) :381-382
[75]   N-Methyl-d-aspartate receptor antagonist MK-801 suppresses glial pro-inflammatory cytokine expression in morphine-tolerant rats [J].
Liu, Ching-Hang ;
Cherng, Chen-Hwen ;
Lin, Shinn-Long ;
Yeh, Chun-Chang ;
Wu, Ching-Tang ;
Tai, Yueh-Hua ;
Wong, Chih-Shung .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2011, 99 (03) :371-380
[76]   Activation of extrasynaptic NMDA receptors induces LTD in rat hippocampal CA1 neurons [J].
Liu, Dan-dan ;
Yang, Qian ;
Li, Sheng-tian .
BRAIN RESEARCH BULLETIN, 2013, 93 :10-16
[77]   Neuroprotective effect of estrogen: Role of nonsynaptic NR2B-containing NMDA receptors [J].
Liu, Shui-bing ;
Zhao, Ming-gao .
BRAIN RESEARCH BULLETIN, 2013, 93 :27-31
[78]   EFFECTS OF THE COMPETITIVE NMDA RECEPTOR ANTAGONIST, CGP-37849, ON ANTICONVULSANT ACTIVITY AND ADVERSE-EFFECTS OF VALPROATE IN AMYGDALA-KINDLED RATS [J].
LOSCHER, W ;
HONACK, D .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1993, 234 (2-3) :237-245
[79]   Antiparkinsonian activity of Ro 25-6981, a NR2B subunit specific NMDA receptor antagonist, in animal models of Parkinson's disease [J].
Löschmann, PA ;
De Groote, C ;
Smith, L ;
Wüllner, U ;
Fischer, G ;
Kemp, JA ;
Jenner, P ;
Klockgether, T .
EXPERIMENTAL NEUROLOGY, 2004, 187 (01) :86-93
[80]   Interactions between ACE inhibitors and classical antiepileptic drugs in the mouse maximal electroshock seizures [J].
Lukawski, Krzysztof ;
Jakubus, Tomasz ;
Janowska, Agnieszka ;
Czuczwar, Stanislaw J. .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2011, 100 (01) :152-156