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神经退行性疾病模型中神经毒性剂诱导的损伤:聚焦谷氨酸受体的作用

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors.

作者信息

Jakaria Md, Park Shin-Young, Haque Md Ezazul, Karthivashan Govindarajan, Kim In-Su, Ganesan Palanivel, Choi Dong-Kug

机构信息

Department of Applied Life Sciences, Graduate School, Konkuk University, Chungju, South Korea.

Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences, Research Institute of Inflammatory Diseases (RID), Konkuk University, Chungju, South Korea.

出版信息

Front Mol Neurosci. 2018 Aug 29;11:307. doi: 10.3389/fnmol.2018.00307. eCollection 2018.

Abstract

Glutamate receptors play a crucial role in the central nervous system and are implicated in different brain disorders. They play a significant role in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although many studies on NDDs have been conducted, their exact pathophysiological characteristics are still not fully understood. In and models of neurotoxic-induced NDDs, neurotoxic agents are used to induce several neuronal injuries for the purpose of correlating them with the pathological characteristics of NDDs. Moreover, therapeutic drugs might be discovered based on the studies employing these models. In NDD models, different neurotoxic agents, namely, kainic acid, domoic acid, glutamate, β--Methylamino-L-alanine, amyloid beta, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, rotenone, 3-Nitropropionic acid and methamphetamine can potently impair both ionotropic and metabotropic glutamate receptors, leading to the progression of toxicity. Many other neurotoxic agents mainly affect the functions of ionotropic glutamate receptors. We discuss particular neurotoxic agents that can act upon glutamate receptors so as to effectively mimic NDDs. The correlation of neurotoxic agent-induced disease characteristics with glutamate receptors would aid the discovery and development of therapeutic drugs for NDDs.

摘要

谷氨酸受体在中枢神经系统中起着至关重要的作用,并与多种脑部疾病有关。它们在神经退行性疾病(如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症)的发病机制中发挥着重要作用。尽管已经对神经退行性疾病进行了许多研究,但其确切的病理生理特征仍未完全了解。在神经毒性诱导的神经退行性疾病模型中,使用神经毒性剂诱导多种神经元损伤,以便将它们与神经退行性疾病的病理特征相关联。此外,基于使用这些模型的研究可能会发现治疗药物。在神经退行性疾病模型中,不同的神经毒性剂,即海藻酸、软骨藻酸、谷氨酸、β-甲基氨基-L-丙氨酸、β淀粉样蛋白、1-甲基-4-苯基-1,2,3,6-四氢吡啶、1-甲基-4-苯基吡啶鎓、鱼藤酮、3-硝基丙酸和甲基苯丙胺,可有效损害离子型和代谢型谷氨酸受体,导致毒性进展。许多其他神经毒性剂主要影响离子型谷氨酸受体的功能。我们讨论了能够作用于谷氨酸受体从而有效模拟神经退行性疾病的特定神经毒性剂。神经毒性剂诱导的疾病特征与谷氨酸受体的相关性将有助于发现和开发用于神经退行性疾病的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65bc/6123546/da4a84167e7f/fnmol-11-00307-g001.jpg

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