DNA damage and neurotoxicity of chronic alcohol abuse.

Exp Biol Med (Maywood)

Department of Pharmacology and Neuroscience, South Plains Alcohol and Addiction Research Center, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.

Published: July 2012

AI Article Synopsis

  • Chronic alcohol abuse can harm the brain, leading to neurodegenerative changes due to unclear mechanisms.
  • One proposed cause is the accumulation of DNA damage which leads to genomic instability and neuron death.
  • The review highlights how dysfunctions in DNA repair and methylation, particularly influenced by alcohol's effects on one-carbon metabolism, contribute to this neurodegeneration.

Article Abstract

Chronic alcohol abuse results in a variety of pathological effects including damage to the brain. The causes of alcohol-induced brain pathology are presently unclear. Several mechanisms of pathogenicity of chronic alcoholism have been proposed, including accumulation of DNA damage in the absence of repair, resulting in genomic instability and death of neurons. Genomic instability is a unified genetic mechanism leading to a variety of neurodegenerative disorders. Ethanol also likely interacts with various metabolic pathways, including one-carbon metabolism (OCM). OCM is critical for the synthesis of DNA precursors, essential for DNA repair, and as a methyl donor for various methylation events, including DNA methylation. Both DNA repair and DNA methylation are critical for maintaining genomic stability. In this review, we outline the role of DNA damage and DNA repair dysfunction in chronic alcohol-induced neurodegeneration.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685494PMC
http://dx.doi.org/10.1258/ebm.2012.011421DOI Listing

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