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酒精成瘾的神经药理学研究——特别强调蛋白质组学方法在新型治疗靶点鉴定中的应用。

Neuropharmacology of Alcohol Addiction with Special Emphasis on Proteomic Approaches for Identification of Novel Therapeutic Targets.

机构信息

Independent Researcher, Bhopal, Madhya Pradesh 462020, India.

Department of Biochemistry, All India Institute of Medical Science, Bhopal, Madhya Pradesh 462020, India.

出版信息

Curr Neuropharmacol. 2023;21(1):119-132. doi: 10.2174/1570159X20666220811092906.

DOI:10.2174/1570159X20666220811092906
PMID:35959616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10193758/
Abstract

Alcohol is a generic pharmacological agent with only a few recognized primary targets. Nmethyl- D-aspartate, gamma-aminobutyric acid, glycine, 5-hydroxytryptamine 3 (serotonin), nicotinic acetylcholine receptors, and L-type Ca channels and G-protein-activated inwardly rectifying K channels are all involved. Following the first hit of alcohol on specific brain targets, the second wave of indirect effects on various neurotransmitter/neuropeptide systems begins, leading to the typical acute behavioral effects of alcohol, which range from disinhibition to sedation and even hypnosis as alcohol concentrations rise. Recent research has revealed that gene regulation is significantly more complex than previously thought and does not fully explain changes in protein levels. As a result, studying the proteome directly, which differs from the genome/transcriptome in terms of complexity and dynamicity, has provided unique insights into extraordinary advances in proteomic techniques that have changed the way we can analyze the composition, regulation, and function of protein complexes and pathways underlying altered neurobiological conditions. Neuroproteomics has the potential to revolutionize alcohol research by allowing researchers to gain a better knowledge of how alcohol impacts protein structure, function, connections, and networks on a global scale. The amount of information collected from these breakthroughs can aid in identifying valuable biomarkers for early detection and improved prognosis of an alcohol use disorder and future pharmaceutical targets for the treatment of alcoholism.

摘要

酒精是一种通用的药理学药物,只有少数几个公认的主要靶点。N-甲基-D-天冬氨酸、γ-氨基丁酸、甘氨酸、5-羟色胺 3(血清素)、烟碱型乙酰胆碱受体和 L 型钙通道以及 G 蛋白激活内向整流钾通道都参与其中。在酒精对特定大脑靶点的首次打击之后,开始了对各种神经递质/神经肽系统的第二轮间接影响,导致酒精的典型急性行为效应,从抑制到镇静,甚至催眠,随着酒精浓度的升高而增加。最近的研究表明,基因调控比以前想象的要复杂得多,并且不能完全解释蛋白质水平的变化。因此,直接研究蛋白质组——在复杂性和动态性方面与基因组/转录组不同——为我们提供了对蛋白质组学技术非凡进展的独特见解,这些技术改变了我们分析改变神经生物学条件下的蛋白质复合物和途径的组成、调控和功能的方式。神经蛋白质组学有可能通过让研究人员更好地了解酒精如何影响蛋白质结构、功能、连接和网络,从而彻底改变酒精研究。从这些突破中收集的信息量可以帮助确定有价值的生物标志物,用于早期检测和改善酒精使用障碍的预后,并为治疗酗酒提供未来的药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/773eab21c0ee/CN-21-119_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/2c2d2c7ec761/CN-21-119_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/c23fa5aa0c54/CN-21-119_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/5c1901b6b05f/CN-21-119_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/773eab21c0ee/CN-21-119_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/2c2d2c7ec761/CN-21-119_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/c23fa5aa0c54/CN-21-119_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/5c1901b6b05f/CN-21-119_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89f3/10193758/773eab21c0ee/CN-21-119_F4.jpg

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本文引用的文献

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Is the Antidepressant Activity of Selective Serotonin Reuptake Inhibitors Mediated by Nicotinic Acetylcholine Receptors?选择性5-羟色胺再摄取抑制剂的抗抑郁活性是由烟碱型乙酰胆碱受体介导的吗?
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