%0 Journal Article
%T The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids
%A Suzanne M. De la Monte
%A Lisa Longato
%A Ming Tong
%A Sarah DeNucci
%A Jack R. Wands
%J International Journal of Environmental Research and Public Health
%D 2009
%I MDPI AG
%R 10.3390/ijerph6072055
%X 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.
%K ethanol
%K insulin resistance
%K ceramides
%K neurodegeneration
%K alcoholic liver disease
%K steatohepatitis
%U http://www.mdpi.com/1660-4601/6/7/2055