GluN2A: A Promising Target for Developing Novel Antidepressants.

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Gang Wang, Wang Qi, Qiu-Hua Liu, Wei Guan
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引用次数: 0

Abstract

Background: Depression is a heterogeneous disorder with high morbidity and disability rates that poses serious problems regarding mental health care. It is now well established that N-methyl D-aspartate receptor (NMDAR) modulators are being increasingly explored as potential therapeutic options for treating depression, although relatively little is known about their mechanisms of action. NMDARs are glutamate-gated ion channels that are ubiquitously expressed in the central nervous system (CNS), and they have been shown to play key roles in excitatory synaptic transmission. GluN2A, the predominant Glu2N subunit of functional NMDARs in neurons, is involved in various physiological processes in the CNS and is associated with diseases such as anxiety, depression, and schizophrenia. However, the role of GluN2A in the pathophysiology of depression has not yet been elucidated.

Methods: We reviewed several past studies to better understand the function of GluN2A in depression. Additionally, we also summarized the pathogenesis of depression based on the regulation of GluN2A expression, particularly its interaction with neuroinflammation and neurogenesis, which has received considerable critical attention and is highly implicated in the onset of depression.

Results: These evidence suggests that GluN2A overexpression impairs structural and functional synaptic plasticity, which contributes to the development of depression. Consequently, this knowledge is vital for the development of selective antagonists targeting GluN2A subunits using pharmacological and molecular methods.

Conclusions: Specific inhibition of the GluN2A NMDAR subunit is resistant to chronic stress-induced depressive-like behaviors, making them promising targets for the development of novel antidepressants.

GluN2A:开发新型抗抑郁药物的前景看好的靶点。
背景:抑郁症是一种异质性疾病,发病率和致残率都很高,给精神卫生保健带来了严重问题。目前,N-甲基-D-天冬氨酸受体(NMDARs)调节剂作为治疗抑郁症的潜在疗法正受到越来越多的关注,但人们对其作用机制的了解却相对较少。NMDARs 是谷氨酸门控离子通道,在中枢神经系统(CNS)中普遍表达,已被证明在兴奋性突触传递中发挥关键作用。神经元中功能性 NMDARs 的主要 Glu2N 亚基 GluN2A 参与了中枢神经系统的各种生理过程,并与焦虑、抑郁和精神分裂症等疾病相关。然而,GluN2A 在抑郁症病理生理学中的作用尚未阐明:方法:为了更好地了解 GluN2A 在抑郁症中的功能,我们回顾了过去的一些研究。此外,我们还总结了基于 GluN2A 表达调控的抑郁症发病机制,尤其是它与神经炎症和神经发生的相互作用,这一点已受到了相当多的关注,并与抑郁症的发病高度相关:这些证据表明,GluN2A 的过度表达会损害突触的结构和功能可塑性,从而导致抑郁症的发生。因此,这些知识对于利用药理学和分子方法开发针对 GluN2A 亚基的选择性拮抗剂至关重要:结论:特异性抑制 GluN2A NMDAR 亚基对慢性应激诱导的抑郁样行为有抵抗作用,使其成为开发新型抗抑郁药物的有前途的靶点。
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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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