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

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 ins...

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Detalles Bibliográficos
Autores principales: de la Monte, Suzanne M., Longato, Lisa, Tong, Ming, DeNucci, Sarah, Wands, Jack R.
Formato: Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738898/
https://www.ncbi.nlm.nih.gov/pubmed/19742171
http://dx.doi.org/10.3390/ijerph6072055
Descripción
Sumario: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.