Fig. 9

Liver-brain axis in R778L mice. Impairment of biliary copper excretion in R778L mice results in progressive accumulation of copper within the liver. This copper accumulation triggers the activation of stress-signaling pathways, including NF-κB, which subsequently leads to inflammatory changes, specifically hepatitis, and the overall accumulation of the extracellular matrix, known as fibrosis, within the liver. Hepatic inflammation further promotes systemic inflammation, which in turn activates microglia and increases the production of pro-inflammatory cytokines, ultimately resulting in neuroinflammation