About this Research Topic

Background

The liver is the most important digestive organ of the human body and the center of human metabolism. It is also vulnerable and can develop various liver diseases including non-alcoholic fatty liver disease (NAFLD, or referred to as MAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD), drug-induced liver injury (DILI) or even hepatocellular carcinoma (HCC) when exposed to excess high-fat diet, alcohol, drugs or viruses. Various liver diseases have become a heavy burden on global healthcare, in which NAFLD carries the highest burden of morbidity among all liver diseases worldwide, with approximately 25% of the global population being estimated to suffer from this disease.

Cell death occurs in various physiological and pathological cellular processes and many different types of programmed cell death (PCD) have been identified, including ferroptosis, autophagy, cuproptosis, apoptosis, pyroptosis, and necroptosis. The death of hepatocytes can trigger and exacerbate chronic hepatic inflammation and fibrosis, leading to the development of cirrhosis and liver cancer. Over the past decade, mounting shreds of evidence have demonstrated that PCD plays an important role in liver pathology. However, the possible forms of PCD and their molecular mechanisms in liver disease remain unclear.

Our understanding of PCD in liver disease has changed dramatically, but whether PCD exerts a beneficial or detrimental effect on liver diseases? What is the specific regulating mechanism of PCD in the liver? What is the potential PCD-related therapeutic target for liver diseases? Do inhibitors or activators of specific PCDs have the potential to be developed as therapeutics? What is the dynamic process of PCD in the liver? What is the crosstalk between PCD and the principal pathogenic features of liver diseases (inflammation, oxidative stress, and mitochondrial dysfunction)? What is the interaction between different kinds of PCDs? There still exist a lot of inquiries to be answered.

This special issue of Frontiers in Pharmacology is dedicated to discovering novel therapeutic drugs for liver diseases by regulating PCD (ferroptosis, autophagy, cuproptosis, apoptosis, pyroptosis, or necroptosis). Studies on the pathological mechanism of various liver diseases from the perspective of PCD (ferroptosis, autophagy, cuproptosis, apoptosis, pyroptosis, or necroptosis) would be interesting. Herein, we aim to provide a theoretical basis for targeting PCD pathways as a novel treatment for liver disease.

• Discovery of novel therapeutic compounds for liver diseases based on PCD regulation
• Novel targets for the treatment of NAFLD by modulating PCD
• The interaction between different kinds of PCD in liver diseases
• Explore the potential mechanism of PCD in liver disease through metabolomics or other cutting-edge technologies
• Inhibitors or activators of specific PCDs that have the potential to be developed as therapeutics
• Crosstalk between PCD and inflammation/oxidative stress/mitochondrial dysfunction in liver
• Liver metabolism and PCD
• The dynamic process of PCD in the liver

Keywords: non-alcoholic fatty liver disease (NAFLD, or referred as MAFLD)；non-alcoholic steatohepatitis (NASH)；alcohol-related liver disease (ALD)；drug induced liver injury (DILI)；hepatocellular carcinoma (HCC)；programmed cell death；ferroptosis；autophagy；cuproptosi

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