Targeting NMDA receptors with an antagonist is a promising therapeutic strategy for treating neurological disorders

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Behavioural Brain Research Pub Date : 2024-08-03 DOI:10.1016/j.bbr.2024.115173
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Abstract

Glutamate activates the NMDARs, significantly affecting multiple processes such as learning, memory, synaptic integration, and excitatory transmission in the central nervous system. Uncontrolled activation of NMDARs is a significant contributor to synaptic dysfunction. Having a properly functioning NMDAR and synapse is crucial for maintaining neuronal communication. In addition, the dysfunction of NMDAR and synapse function could contribute to the development of neurological disorders at the neuronal level; hence, targeting NMDARs with antagonists in the fight against neurological disorders is a promising route. Recently published results from the animal study on different kinds of brain diseases like stroke, epilepsy, tinnitus, ataxia, Alzheimer’s disease, Parkinson's disease, and spinal cord injury have demonstrated promising therapeutic scopes. Several NMDA receptor antagonists, such as memantine, MK801, ketamine, ifenprodil, gacyclidine, amantadine, agmatine, etc., showed encouraging results against different brain disease mouse models. Given the unique expression of different subunits of the well-organized NMDA receptor system by neurons. It could potentially lead to the development of medications specifically targeting certain receptor subtypes. For a future researcher, conducting more targeted research and trials is crucial to fully understand and develop highly specific medications with good clinical effects and potential neuroprotective properties.

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用拮抗剂靶向 NMDA 受体是治疗神经系统疾病的一种很有前景的治疗策略。
谷氨酸可激活 NMDARs,对中枢神经系统的学习、记忆、突触整合和兴奋传递等多个过程产生重大影响。NMDARs 的失控激活是导致突触功能障碍的一个重要因素。拥有正常功能的 NMDAR 和突触对于维持神经元交流至关重要。此外,NMDAR 和突触功能的失调可能会导致神经元水平的神经系统疾病;因此,在对抗神经系统疾病的过程中,使用拮抗剂靶向 NMDAR 是一条很有前景的途径。最近发表的关于中风、癫痫、耳鸣、共济失调、阿尔茨海默病、帕金森病和脊髓损伤等各种脑部疾病的动物研究结果表明,这些疾病具有广阔的治疗前景。一些 NMDA 受体拮抗剂,如美金刚、MK801、氯胺酮、ifenprodil、加西奎丁、金刚烷胺、阿甘马汀等,对不同的脑疾病小鼠模型显示出令人鼓舞的结果。鉴于神经元在组织完善的 NMDA 受体系统中不同亚基的独特表达方式。这有可能导致开发出专门针对某些受体亚型的药物。对于未来的研究人员来说,开展更有针对性的研究和试验对于充分了解和开发具有良好临床效果和潜在神经保护特性的高度特异性药物至关重要。
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来源期刊
Behavioural Brain Research
Behavioural Brain Research 医学-行为科学
CiteScore
5.60
自引率
0.00%
发文量
383
审稿时长
61 days
期刊介绍: Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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