Alcohol Res Health 30:5–13, PubMed These results suggest an important role of XO in HFD-induced NAFLD and hyperuricemia. 1g) relative to healthy subjects (Additional file 1: Figure S1A, B). J Neurol Sci 156:172–176. These metabolic changes could be one mechanism responsible for the increased gout incidences observed in alcoholic individuals (Ka et al., 2006; Lieber, 2005; Yamamoto, Moriwaki, & Takahashi, 2005; Zakhari & Li, 2007). As classified by the World Health Organization (WHO), alcohol use is the third-highest health risk factor in developed countries and the greatest risk factor in developing countries,  and its aldehydic metabolite, acetaldehyde, is classified as a class I carcinogen . A TATA-like sequence (TTATAAAA) and a CAAT-like sequence (GTCATCAT) are located 473 and 515 bp, respectively, upstream from the translation initiation codon. https://doi.org/10.2174/157015909787602823, Wang B, Wang J, Zhou S, Tan S, He X, Yang Z, Xie YC, Li S, Zheng C, Ma X (2008) The association of mitochondrial aldehyde dehydrogenase gene (ALDH2) polymorphism with susceptibility to late-onset Alzheimer's disease in Chinese. e) Levels of Interlukin-1β release at 6 h were determined by immunoblotting in primary astrocytes in the presence or absence of Alda-1 (20 μM; 50 mM Ethanol). https://doi.org/10.1126/science.1171091, Collaborators GBDA (2018) Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Ulrich M. Zanger, ... Chang S. Ryu, in Advances in Pharmacology, 2018. Here, using an unbiased proteomic search, we identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models. e) Malondialdehyde content was determined using MDA lipid peroxidation assay in total brain homogenate; Veh – Vehicle; A – Alda-1. Functional polymorphisms in ethanol metabolism: ADH1B His48Arg and ALDH2 Glu487Lys. These changes correlated with a substantially reduced oxygen consumption and a shift towards glycolysis (Fig. Mice null for ALDH1a1 and ALDH2 exhibit Parkinson's disease-like age-dependent deficits in motor performance and significant increase in biogenic aldehydes. 2019 Jan;39(1):48-62. doi: 10.1161/ATVBAHA.118.311714. Furthermore, Alda-1 reduced the accumulation of the neurotoxic proteins Aβ42 and phosphorylated tau after chronic ethanol exposure and blunted synaptic loss (measured by determining synaptophysin levels), which was associated with reduced activation of the pro-apoptotic caspase 3 (Fig. We therefore suggest that the susceptibility to Alzheimer’s disease in subjects carrying ALDH2*2 mutation increases if they consume alcoholic beverages and that reduction of the aldehydic load in patients without or with ALDH2 inactivating mutation may help slowing down disease progression. b) Measurement of mitochondrial ROS using MitoSOX™ in primary neurons, treated as in B. c) Caspase-3 activity was determined in total lysates using a fluorometric assay based on the cleavage of substrate DEVD-AFC in primary neurons in the presence or absence of Alda-1 (20 μM/24 h; 50 mM Ethanol). Suliga E, Kozieł D, Ciesla E, Rebak D, Głuszek-Osuch M, Głuszek S. Nutrients. https://doi.org/10.1073/pnas.1414657112, Chen J, Huang W, Cheng CH, Zhou L, Jiang GB, Hu YY (2019) Association Between Aldehyde dehydrogenase-2 Polymorphisms and Risk of Alzheimer's Disease and Parkinson's Disease: A Meta-Analysis Based on 5,315 Individuals. https://doi.org/10.1093/eurheartj/ehr304, Frost GR, Li YM (2017) The role of astrocytes in amyloid production and Alzheimer's disease. As ALDH2 is critical in reducing aldehydic load, especially that induced by ethanol metabolism, and even in the absence of ethanol exposure, ALDH2−/− knockout mice have increased 4HNE levels and develop AD-like pathology . NIH Ethanol increases metabolic dysfunction of Alzheimer’s disease (AD) patient-derived fibroblasts that is rescued by ALDH2 activation. f) IL-1α levels were measured in total brain homogenate using ELISA kit; Veh – Vehicle; A – Alda-1. reported that ADH1A variation may contribute to the genetic component of variation in personality trait and substance abuse disorder . In addition to its critical role in ethanol metabolism, ALDH2 plays a key role in oxidizing endogenous aldehydic products that arise from lipid peroxidation under oxidative stress, such as 4-HNE and MDA. For 4-HNE, Lipid Peroxidation (4-HNE) Assay Kit (Abcam) was used. ALDH2 deficiency is known to increase oxidative stress. Therefore, ALDH2 activity contributes to astrocytic function and their inflammatory state. β-actin was used as loading control. https://doi.org/10.1016/j.cld.2012.08.002, Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F (2018) Oxidative stress and the amyloid beta peptide in Alzheimer's disease. PLoS Med 6:e50. Scheme of the Mendelian randomization…, Fig. -. Redox Biol 4:193–199. Adermark L, Bowers MS (2016) Disentangling the Role of Astrocytes in Alcohol Use Disorder. As over 40% of the world population and about 70% of adults in Western countries consume ethanol-containing beverages according to the Global status report on alcohol and health 2018, we next determined whether ethanol exposure further increases metabolic dysfunction. 4-HNE and MDA significantly increased in ALDH2*2 and WT mice after chronic ethanol exposure (Fig. PubMed Central ALDH2---The Genetic Polymorphism and Enzymatic Activity Regulation: Their Epidemiologic and Clinical Implications. β-actin was used as loading control. n = 3 independent biological replicates; probability by one-way ANOVA (with Holm-Sidak post hoc test). d) Levels of cellular COX-2 at 6 h were determined by immunoblotting in primary astrocytes in the presence or absence of Alda-1 (20 μM; 50 mM Ethanol). d) MCP-1 levels in total brain homogenate were measured using mouse MCP1 ELISA kit; Veh – Vehicle; A – Alda-1. , Monomer of human aldehyde dehydrogenase 2 (, Pathology (aldehyde dehydrogenase deficiency), "Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily", "Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology", "Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review", "Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men", "Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics", "Prognostic value of aldehyde dehydrogenase 1 (ALDH1) in invasive breast carcinomas", "Neurodegeneration and aldehyde load: from concept to therapeutics", "Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease", "Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: implications for Parkinson's disease", "Deuterium-reinforced polyunsaturated fatty acids improve cognition in a mouse model of sporadic Alzheimer's disease", Branched-chain alpha-keto acid dehydrogenase complex, https://en.wikipedia.org/w/index.php?title=Aldehyde_dehydrogenase&oldid=990275936, Creative Commons Attribution-ShareAlike License, This page was last edited on 23 November 2020, at 20:04.
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