Targeting alcohol-detoxifying enzymes

A study finds that knockout of an alcohol metabolism gene in the liver of mice decreases excessive but not moderate alcohol seeking activity. The aldehyde dehydrogenase-2 (ALDH-2) enzyme is a target for treating alcohol use disorders, given that the enzyme clears the alcohol metabolite acetaldehyde, which causes undesirable side effects of alcohol consumption. The liver is a source of ALDH-2 and alcohol processing, but the ALDH-2 contributions of other organs are unclear. Bin Gao and colleagues knocked out the gene responsible for producing ALDH-2 in mice, both throughout the organism and specifically in the liver. After exposure to ethanol, both groups of knockout mice exhibited higher acetaldehyde levels than wild-type mice, with whole-organism knockout mice exhibiting much higher levels than liver knockout mice. In tests of ethanol consumption, whole-organism knockout mice largely preferred not to drink ethanol, whereas liver knockout mice showed reduced preference for high ethanol concentrations, but not for low concentrations. According to the authors, the results suggest that multiple organs contribute a cumulative amount of ALDH-2, and that specifically targeting the enzyme in the liver may reduce excessive drinking behavior without affecting moderate drinking.

Article #19-08137: “Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking,” by Adrien Guillot et al.

MEDIA CONTACT: Bin Gao, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD; tel: 301-443-3998; e-mail:

[email protected]

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