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The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids

Author

Listed:
  • Suzanne M. De la Monte

    (Division of Neuropathology, Brown University, Providence, RI, USA)

  • Lisa Longato

    (The Liver Research Center, Brown University, Providence, RI, USA
    Rhode Island Hospital, Brown University, Providence, RI, USA)

  • Ming Tong

    (Division of Gastroenterology, Brown University, Providence, RI, USA
    Department of Medicine, Brown University, Providence, RI, USA
    The Liver Research Center, Brown University, Providence, RI, USA
    Rhode Island Hospital, Brown University, Providence, RI, USA)

  • Sarah DeNucci

    (Department of Medicine, Brown University, Providence, RI, USA
    Rhode Island Hospital, Brown University, Providence, RI, USA
    The Warren Alpert Medical School, Brown University, Providence, RI, USA)

  • Jack R. Wands

    (Division of Gastroenterology, Brown University, Providence, RI, USA
    Department of Medicine, Brown University, Providence, RI, USA
    The Liver Research Center, Brown University, Providence, RI, USA
    Rhode Island Hospital, Brown University, Providence, RI, USA)

Abstract

Alcohol abuse causes progressive toxicity and degeneration in liver and brain due to insulin resistance, which exacerbates oxidative stress and pro-inflammatory cytokine activation. Alcohol-induced steatohepatitis promotes synthesis and accumulation of ceramides and other toxic lipids that cause insulin resistance. Ceramides can readily cross the blood-brain barrier, and ceramide exposure causes neurodegeneration with insulin resistance and oxidative stress, similar to the effects of alcohol. Therefore, in addition to its direct neurotoxic effects, alcohol misuse establishes a liver-brain axis of neurodegeneration mediated by toxic lipid trafficking across the blood-brain barrier, leading to progressive white matter degeneration and cognitive impairment.

Suggested Citation

  • Suzanne M. De la Monte & Lisa Longato & Ming Tong & Sarah DeNucci & Jack R. Wands, 2009. "The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids," IJERPH, MDPI, vol. 6(7), pages 1-21, July.
    • Handle: RePEc:gam:jijerp:v:6:y:2009:i:7:p:2055-2075:d:5408
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    Cited by:

    1. Hiroshi Mitoma & Mario Manto & Aasef G. Shaikh, 2021. "Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum," IJERPH, MDPI, vol. 18(16), pages 1-14, August.

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