Targeting cell death in NAFLD: mechanisms and targeted therapies

Area of Science:

• Hepatology
• Cell Biology
• Molecular Mechanisms of Disease

Background:

• Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH).
• NAFLD pathogenesis involves lipid accumulation, inflammation, fibrosis, and diverse cell death modalities.
• Current NAFLD/NASH therapies primarily target fatty acid metabolism and inflammation, with limited focus on cell death signaling.

Purpose of the Study:

• To review the roles of apoptosis, necroptosis, pyroptosis, and ferroptosis in NAFLD progression.
• To elucidate molecular mechanisms of pathogenic factors inducing cell death in NAFLD.
• To summarize cell death-targeted therapies for NAFLD treatment.

Main Methods:

• Literature review of preclinical and clinical studies on NAFLD/NASH.
• Analysis of molecular mechanisms underlying cell death induction in NAFLD.
• Evaluation of therapeutic strategies targeting cell death pathways.

Main Results:

• Identified four key cell death types (apoptosis, necroptosis, pyroptosis, ferroptosis) in NAFLD progression.
• Detailed mechanisms by which free fatty acids and LPS trigger cell death in NAFLD.
• Highlighted the potential of cell death-targeted therapies in preclinical and clinical settings.

Conclusions:

• Cell death plays a critical role throughout NAFLD pathogenesis.
• Targeting specific cell death pathways presents a novel therapeutic avenue for NAFLD and NASH.
• Further research into cell death mechanisms can unlock new treatment strategies.