Multiple predicted NAFLD-related protein targets

Multiple predicted NAFLD-related protein targets refers to a heterogeneous group of biological molecules identified through computational biology, network analysis, or experimental screening as potential therapeutic points for Non-Alcoholic Fatty Liver Disease (NAFLD), now termed Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (Rinella et al., 2023). This designation does not represent a single protein or receptor but rather a collection of candidates involved in the complex, multi-factorial pathogenesis of the disease, including hepatic steatosis, inflammation, and fibrosis (Polyzos et al., 2020). Common proteins within these predicted sets include Acetyl-CoA Carboxylase (ACC), Farnesoid X Receptor (FXR), and Peroxisome Proliferator-Activated Receptors (PPARs), which regulate lipid metabolism and inflammatory signaling (Younossi et al., 2019). Because the disease involves 'multiple parallel hits,' researchers often target several of these proteins simultaneously using combination therapies or multi-target agents to achieve clinical efficacy (Friedman et al., 2018). Consequently, there is no single mechanism of action or safety profile for this collective term; instead, it serves as a conceptual framework for drug discovery efforts aimed at reversing the progression of steatohepatitis (Anstee et al., 2019).

Other names

NAFLD-related targetsMASLD-related targetsNASH-related protein targetsPredicted steatohepatitis targets

The mechanisms of action for drugs targeting these predicted proteins are diverse and include the modulation of thyroid hormone signaling, activation of nuclear receptors to regulate bile acid synthesis, and agonism of incretin receptors to improve insulin sensitivity and reduce hepatic fat (Friedman et al., 2018; Younossi et al., 2019).