Levodopa and the dopamine receptor D1-Hippo/yes-associated protein axis: A novel therapeutic avenue for liver fibrosis

Abstract

Liver fibrosis remains a major global health challenge with limited therapeutic options. In their recent study, Wang et al report that levodopa, a dopamine precursor widely used in Parkinson’s disease, significantly attenuates carbon tetrachloride-induced liver fibrosis in rats by enhancing dopamine receptor D1 expression and activating the Hippo signaling pathway, leading to phosphorylation and inactivation of yes-associated protein 1. This discovery links G-protein-coupled receptor signaling to Hippo pathway regulation in hepatic fibrosis. The work highlights the dopamine receptor D1-Hippo/yes-associated protein 1 axis as a promising antifibrotic mechanism and introduces levodopa as a potential repurposing candidate for chronic liver disease. With its established safety and affordability, levodopa offers a rapidly translatable strategy that warrants validation in human tissues and diverse fibrosis models. Here, we place these findings in the broader context of G-protein-coupled receptor regulation of hepatic stellate cell activation, discuss translational opportunities for levodopa in liver fibrosis, and propose future directions to validate this pathway across disease models and clinical settings.

Keywords: Levodopa; Liver fibrosis; Dopamine receptor D1; Hippo signaling pathway; Yes-associated protein; Drug repurposing; Hepatic stellate cell; G-protein coupled receptor

Core Tip: This editorial highlights a novel mechanistic insight from a recent study by Wang et al, which identifies the dopamine precursor levodopa, a mainstay Parkinson’s disease therapy, as a potent inhibitor of liver fibrosis in experimental models. The antifibrotic effect is mediated through activation of dopamine receptor D1, which stimulates the Hippo signaling pathway to inactivate the profibrotic transcriptional coactivator yes-associated protein. With its decades-long clinical use, safety record, and affordability, levodopa offers translational advantages and positions this neurologic drug as a potentially rapid and cost-effective therapy for chronic liver disease.