Emerging importance of ALDH2 in liver diseases and its potential therapeutic role
Sheng Wang1, Shiqiang Xu2, Guoqing Xia2
1Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, Institute for Liver Diseases of Anhui Medical University, Anhui Prevention and Control Engineering Research Center for Steatosis Hepatis, School of Pharmaceutical Sciences, Anhui Medical University, Hefei, Anhui Province 230032, China; Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China.
Abstract:
Acetaldehyde dehydrogenase 2 (ALDH2) is an essential metabolic enzyme in mitochondria, responsible for eliminating acetaldehyde and other toxic aldehydes. In the liver, ALDH2 not only has metabolic regulatory functions, but is also closely related to the occurrence and development of various liver diseases. In recent years, studies have demonstrated that the abnormal expression or genetic polymorphism of ALDH2 may be involved in the progression of alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis, toxin-induced liver injury, hepatocellular carcinoma (HCC) and liver ischemia-reperfusion injury (IRI) by triggering acetaldehyde accumulation and oxidative stress, activating inflammatory response mechanisms and affecting metabolic processes. Therefore, it is of great significance to reveal the key regulatory mechanisms and roles of ALDH2 and its mediated related signaling pathways in liver diseases. Currently, the discovery and development of drugs targeting ALDH2 are receiving increasing attention, and several modulators of ALDH2 have been identified, providing promising directions for the clinical treatment of liver diseases. This review aims to summarize the biochemical and biological functions of ALDH2, as well as its role in liver diseases, and explore its potential and application prospects as a therapeutic target, which will help develop therapeutic strategies for liver diseases.
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