酒精使用障碍中的酒精代谢:一个潜在的治疗靶点。

IF 2.1 4区 医学 Q3 SUBSTANCE ABUSE Alcohol and alcoholism Pub Date : 2024-01-11 DOI:10.1093/alcalc/agad077
Taylor Lehner, Bin Gao, Bryan Mackowiak
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引用次数: 0

摘要

乙醇代谢在身体如何感知和体验酒精消费中起着至关重要的作用,有证据表明,调节乙醇代谢可以改变酒精使用障碍(AUD)的风险。在这篇综述中,我们结合临床前和临床研究结果,探讨乙醇代谢(主要通过酒精脱氢酶和醛脱氢酶2 (ALDH2))如何影响饮酒行为。我们讨论了酒精脱氢酶和ALDH2多态性如何改变AUD的风险,以及我们是否可以利用这些知识来设计改变乙醇代谢的AUD干预措施。我们详细介绍了使用双硫仑、RNAi策略和葛根/异黄酮来抑制ALDH2和增加乙醛,理想情况下导致饮酒行为的减少。此外,我们涵盖了最近的临床前证据,表明除了增加乙醛介导的厌恶之外,其他策略可以减少乙醇消耗,提供其他潜在的以代谢为中心的治疗靶点。然而,调节乙醇代谢具有固有的风险,我们指出了一些关键领域,需要更多的数据来减轻这些潜在的不利影响。最后,我们对通过调节乙醇代谢治疗AUD的未来提出了自己的看法。
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Alcohol metabolism in alcohol use disorder: a potential therapeutic target.

Ethanol metabolism plays an essential role in how the body perceives and experiences alcohol consumption, and evidence suggests that modulation of ethanol metabolism can alter the risk for alcohol use disorder (AUD). In this review, we explore how ethanol metabolism, mainly via alcohol dehydrogenase and aldehyde dehydrogenase 2 (ALDH2), contributes to drinking behaviors by integrating preclinical and clinical findings. We discuss how alcohol dehydrogenase and ALDH2 polymorphisms change the risk for AUD, and whether we can harness that knowledge to design interventions for AUD that alter ethanol metabolism. We detail the use of disulfiram, RNAi strategies, and kudzu/isoflavones to inhibit ALDH2 and increase acetaldehyde, ideally leading to decreases in drinking behavior. In addition, we cover recent preclinical evidence suggesting that strategies other than increasing acetaldehyde-mediated aversion can decrease ethanol consumption, providing other potential metabolism-centric therapeutic targets. However, modulating ethanol metabolism has inherent risks, and we point out some of the key areas in which more data are needed to mitigate these potential adverse effects. Finally, we present our opinions on the future of treating AUD by the modulation of ethanol metabolism.

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来源期刊
Alcohol and alcoholism
Alcohol and alcoholism 医学-药物滥用
CiteScore
4.70
自引率
3.60%
发文量
62
审稿时长
4-8 weeks
期刊介绍: About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.
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