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Int. J. Environ. Res. Public Health 2009, 6(7), 2055-2075; doi:10.3390/ijerph6072055

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

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.
Received: 24 June 2009 / Accepted: 16 July 2009 / Published: 23 July 2009
(This article belongs to the Special Issue Alcohol and Public Health)
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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. 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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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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