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

International Journal of Environmental Research and Public Health

Suzanne M. de la Monte¹  Lisa Longato³  Ming Tong²  Sarah DeNucci⁴ 

[1] Division of Neuropathology, Brown University, Providence, RI, USA;Division of Gastroenterology, Brown University, Providence, RI, USA;The Liver Research Center, Brown University, Providence, RI, USA;Department of Medicine, Brown University, Providence, RI, USA

关键词: ethanol;    insulin resistance;    ceramides;    neurodegeneration;    alcoholic liver disease;    steatohepatitis;   

DOI  :  10.3390/ijerph6072055

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.