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• De la Monte, SM.
• Longato, L
• Tong, M
• DeNucci, S
• Wands, JR.
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• De la Monte, SM.
• Longato, L
• Tong, M
• DeNucci, S
• Wands, JR.
• [+] on PubMed
• De la Monte, SM.
• Longato, L
• Tong, M
• DeNucci, S
• Wands, JR.

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

Article

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

Suzanne M. De la Monte^1,3-8,* , Lisa Longato^6,7 , Ming Tong^2,3,6,7,8 , Sarah DeNucci^3,7,8  and Jack R. Wands^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.

Received: 24 June 2009 / Accepted: 16 July 2009 / Published: 23 July 2009

(This article belongs to the Special Issue Alcohol and Public Health)

Download PDF Full-Text [762 KB, uploaded 23 July 2009 07:58 CEST]

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.

Keywords: ethanol; insulin resistance; ceramides; neurodegeneration; alcoholic liver disease; steatohepatitis

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