Non-Alcoholic Fatty Liver Disease (NAFLD)
Non-Alcoholic Fatty Liver Disease (NAFLD), which has recently been renamed Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a common chronic liver condition characterized by excessive fat accumulation in the liver. Protheragen provides MyD88-focused drug discovery services to mitigate liver inflammation and fibrosis, addressing the transition from steatosis to MASH and preventing disease progression.
Introduction to NAFLD
MASLD has an exponentially ever rising prevalence all over the world because of the increasing prevalence of obesity and type 2 diabetes as well as metabolic syndrome. The condition has posed a problem to the international population from the perspective of healthcare, as well as posing a longterm risk to the liver. While steatosis has always been regarded as the primary feature, currently, inflammation (MASH) is considered one of the most important processes in the progression and advancement of hepatic damage and fibrosis.
Pathogenesis of NAFLD
Progression of NAFLD is influenced by metabolic processes (lipotoxicity and insulin sensitivity) coupled with activation of innate immunity such as MyD88-dependent TLR pathways, stimulated by gut PAMPs (LPS) and DAMPs (free fatty acids). This signaling circuitry potentiates liver inflammation (TNF-α, IL-6, NLRP3) and hepatic stellate cell activation thus accelerating fibrosis. MyD88 also connects gut dysbiosis with liver damage, worsening steatosis and inflammation in a cyclic manner.
Fig.1 The different stages of non-alcoholic fatty liver disease (NAFLD). (Guo et al., 2022)MyD88-Targeted Therapeutic Development for NAFLD
| Therapeutic Strategy | Mechanism of Action | Key Findings | Development Stage |
| ST2825 | Selective inhibitor of MyD88 homodimerization Blocks downstream TLR4/MyD88 signaling |
Reduces hepatic steatosis and fibrosis in HFD-fed mice Decreases pro-inflammatory cytokine levels |
Preclinical |
| Artesunate | Downregulates TLR4/MyD88/NF-κB axis Modulates hepatic lipid metabolism |
Attenuates hepatic steatosis and inflammation in HFD mouse models Reduces oxidative stress markers |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen's services include MyD88-targeted therapeutic discovery and advanced disease models development for MASLD/NAFLD. Our platform integrates liver-specific in vitro and in vivo models for high-throughput screening of MyD88 signaling modulators, TLR/IL-1R-driven liver inflammation, steatosis, and fibrotic pathways.
Therapeutic Discovery Platform for NAFLD
Protheragen's MyD88 discovery platform for MASLD/NAFLD leverages immune-liver crosstalk models to rebalance dysregulated innate immune interactions driving liver inflammation and fibrosis. The platform accelerates preclinical validation by targeting MyD88-dependent inflammatory networks and mitigating fibrogenesis through novel inhibitors, degraders, or biologics, while synergizing with existing metabolic or liver-directed strategies.
Disease Models Development for NAFLD
Protheragen provides a complete set of preclinical models for MASLD/NAFLD, including cell-based models, organoid models, and animal models that recapitulate key aspects of metabolic dysfunction, steatosis, inflammation (MASH), and fibrotic pathophysiology.
- Primary Hepatocyte Cultures
- Kupffer Cell / Liver Macrophage Cultures
- Hepatic Stellate Cell Cultures
- Co-culture Models
- 3D Liver Organoid Models
- DSS-LPS NASH Model
- Liver-TLR4 Transgenic Mice
- LPS/D-GalN ACLI Model
- HFHCD Mice
- CDAA Diet Rats
Protheragen delivers end-to-end solutions for MyD88-related diseases, integrating disease model development, pharmacokinetics and drug safety evaluation. Other focuses include investigator-initiated trials aimed to accelerate preclinical-to-clinical translation.
If you are interested in our services, please don't hesitate to contact us.
References
- Guo, X., et al. "Non-Alcoholic Fatty Liver Disease (Nafld) Pathogenesis and Natural Products for Prevention and Treatment." Int J Mol Sci 23.24 (2022).
- Rong, L., et al. "Advancements in the Treatment of Non-Alcoholic Fatty Liver Disease (Nafld)." Front Endocrinol (Lausanne) 13 (2022): 1087260.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.