ArticleNature communications2023
A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Hydrogel microneedles loaded with engineered extracellular vesicles accelerate diabetic wound healing by promoting angiogenesis and modulating macrophage polarization.Materials today. Bio · 2026Article
- Targeting ALDH2 with Alda-1 to reverse cisplatin resistance in lung adenocarcinoma.Cancer chemotherapy and pharmacology · 2026Article
- Review
- Biphasic regulation of myogenesis by ALDH2, aldosterone, and oxidative stress.Pflugers Archiv : European journal of physiology · 2026Article
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- Diurnal Regulation and Gene-Specific Vulnerability of Oxidative Alcohol-Metabolizing Enzymes to Circadian Disruption.International journal of molecular sciences · 2026Article
- ALDH2 protects against dopaminergic neuronal cell ferroptosis by enhancing the enzyme activity of PRDX6 in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Global research landscapes of ALDH2 and cancer revealed by bibliometric analysis.Discover oncology · 2025Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Genetic Polymorphisms ofInternational journal of molecular sciences · 2025Review
- Design, Synthesis, and Protective Effect Evaluation on Myocardial Ischemia of New Triazole Aldehyde Dehydrogenase 2 Activators.ACS medicinal chemistry letters · 2025Article
- Metabolic diseases in the East Asian populations.Nature reviews. Gastroenterology & hepatology · 2025Review
- ALDH2 Enzyme Deficiency in Diabetic Cardiomyopathy.International journal of molecular sciences · 2025Review
- Mitochondrial aldehyde dehydrogenase restores the migratory capacity inhibited by high glucose-induced hyperosmolality.Scientific reports · 2025Article
- Multitrait Genetic Analysis Identifies Novel Pleiotropic Loci for Depression and Schizophrenia in East Asians.Schizophrenia bulletin · 2025Article
- Personalized Lifestyle Interventions for Prevention and Treatment of Obesity-Related Cancers: A Call to Action.Cancers · 2025Article
- Transcriptome analysis of liver injury of fatty liver disease induced by ALDH2 deficiency.Scientific reports · 2025Article
- Analysis and Validation of Mitophagy-Related Genes in Diabetic Foot Ulcers.Journal of inflammation research · 2025Article
- Proteo-genomic analyses in relatively lean Chinese adults identify proteins and pathways that affect general and central adiposity levels.Communications biology · 2024Article
- Aldehyde dehydrogenase 2 preserves kidney function by countering acrolein-induced metabolic and mitochondrial dysfunction.JCI insight · 2024Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Obesity and type 2 diabetes have reached pandemic proportion. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal. A missense Glu504Lys mutation of the ALDH2 gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We find that male Aldh2 knock-in mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver due to reduced adaptive thermogenesis and energy expenditure. We find reduced activity of ALDH2 of the brown adipose tissue from the male Aldh2 homozygous knock-in mice. Proteomic analyses of the brown adipose tissue from the male Aldh2 knock-in mice identifies increased 4-hydroxynonenal-adducted proteins involved in mitochondrial fatty acid oxidation and electron transport chain, leading to markedly decreased fatty acid oxidation rate and mitochondrial respiration of brown adipose tissue, which is essential for adaptive thermogenesis and energy expenditure. AD-9308 is a water-soluble, potent, and highly selective ALDH2 activator. AD-9308 treatment ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and knock-in mice. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for metabolic diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.