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Article

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

by 1,*,3-8, 6,7, 2,3,6,7,8, 3,7,8 and 2,3,6,7,8
1
Division of Neuropathology, Brown University, Providence, RI, USA
2
Division of Gastroenterology, Brown University, Providence, RI, USA
3
Department of Medicine, Brown University, Providence, RI, USA
4
Department of Pathology, Brown University, Providence, RI, USA
5
Department of Neurology, Brown University, Providence, RI, USA
6
The Liver Research Center, Brown University, Providence, RI, USA
7
Rhode Island Hospital, Brown University, Providence, RI, USA
8
The Warren Alpert Medical School, Brown University, Providence, RI, USA
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2009, 6(7), 2055-2075; https://doi.org/10.3390/ijerph6072055
Received: 24 June 2009 / Accepted: 16 July 2009 / Published: 23 July 2009
(This article belongs to the Special Issue Alcohol and Public Health)
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. View Full-Text
Keywords: ethanol; insulin resistance; ceramides; neurodegeneration; alcoholic liver disease; steatohepatitis ethanol; insulin resistance; ceramides; neurodegeneration; alcoholic liver disease; steatohepatitis
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MDPI and ACS Style

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. https://doi.org/10.3390/ijerph6072055

AMA Style

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. https://doi.org/10.3390/ijerph6072055

Chicago/Turabian Style

De la Monte, Suzanne M., Lisa Longato, Ming Tong, Sarah DeNucci, and Jack R. Wands 2009. "The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids" International Journal of Environmental Research and Public Health 6, no. 7: 2055-2075. https://doi.org/10.3390/ijerph6072055

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