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.
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De la Monte, S.M.; Longato, L.; Tong, M.; DeNucci, S.; Wands, J.R. The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids. Int. J. Environ. Res. Public Health 2009, 6, 2055-2075.
De la Monte SM, Longato L, Tong M, DeNucci S, Wands JR. The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids. International Journal of Environmental Research and Public Health. 2009; 6(7):2055-2075.
De la Monte, Suzanne M.; Longato, Lisa; Tong, Ming; DeNucci, Sarah; Wands, Jack R. 2009. "The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids." Int. J. Environ. Res. Public Health 6, no. 7: 2055-2075.