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Publications

Journal Article Review Epublish

PubMed: 40227291 DOI: 10.3390/antiox14030302

Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage.

Antioxidants (Basel) 14(3)

Authors: Leon Ruiter-Lopez, Mohammed A S Khan, Xin Wang, Byoung-Joon Song

Affiliations

  • Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.
  • Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Excessive alcohol consumption significantly impacts human health, particularly the brain, due to its susceptibility to oxidative stress, which contributes to neurodegenerative conditions. Alcohol metabolism in the brain occurs primarily via catalase, followed by CYP2E1 pathways. Excess alcohol metabolized by CYP2E1 generates reactive oxygen/nitrogen species (ROS/RNS), leading to cell injury via altering many different pathways. Elevated oxidative stress impairs autophagic processes, increasing post-translational modifications and further exacerbating mitochondrial dysfunction and ER stress, leading to cell death. The literature highlights that alcohol-induced oxidative stress disrupts autophagy and mitophagy, contributing to neuronal damage. Key mechanisms include mitochondrial dysfunction, ER stress, epigenetics, and the accumulation of oxidatively modified proteins, which lead to neuroinflammation and impaired cellular quality control. These processes are exacerbated by chronic alcohol exposure, resulting in the suppression of protective pathways like NRF2-mediated antioxidant responses and increased susceptibility to neurodegenerative changes in the brain. Alcohol-mediated neurotoxicity involves complex interactions between alcohol metabolism, oxidative stress, and autophagy regulation, which are influenced by various factors such as drinking patterns, nutritional status, and genetic/environmental factors, highlighting the need for further molecular studies to unravel these mechanisms and develop targeted interventions.

MeSH

Cells, Autophagy, Stress, Physiological, Brain, Oxidative Stress, Antioxidants, Ethanol, Mitophagy

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