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The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases
Yufei Chen1, Runxuan Zhou2, Tinghui Zhao3
1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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The ADAM (a disintegrin and metalloproteinase) family, a class of transmembrane proteases with multiple biological functions, plays pivotal roles in processes of proteolytic ectodomain shedding, which are enabled by its unique structural characteristics. In recent years, advancements in molecular biology techniques have led to the progressive identification of shed substrates from ADAM members, whose aberrant expression or dysregulation is closely implicated in the initiation and progression of liver diseases. This review systematically outlines the core domain architecture and biological functions of ADAM proteases, summarizes their major shedding substrates, and elaborates the molecular mechanisms by which the ADAM members regulate the pathophysiological processes of liver diseases. By synthesizing current research advances and unresolved challenges, this work aims to establish a theoretical foundation and propose future research directions for the development of ADAM-based diagnostic markers, targeted therapeutics, and clinical translation in liver diseases.
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