ADAMs (A Disintegrin-like And Metalloproteinases), ADAMTSs (ADAM with Thrombospondin-like motifs) and Astacins are members of the metzincin superfamily of zinc-containing metalloproteinases. ADAMs and ADAMTSs are membrane-bound and secreted proteases, respectively, while astacins include both secreted and membrane-bound members. In addition to the metalloproteinase domain, containing the consensus sequence for binding the catalytic zinc ion, all these families are equipped with non-catalytic, ancillary domains involved in substrate recognition and processing.

ADAMs are characterized by their ability to shed a variety of substrates from the plasma membrane, while the proteolytic activity of extracellular matrix-associated ADAMTSs is essential for maintaining the biophysical properties of a variety of tissues. ADAMs and ADAMTSs participate in many biological processes such as inflammation, cell invasion and migration, as well as turnover of extracellular matrix molecules, while astacins are involved in digestion, cytokine activation and extracellular coat degradation (hatching).

These three metalloproteinase subfamilies have been considered as promising pharmaceutical targets in diseases such as cancer, neurodegeneration, coronary artery disease and degenerative joint disorders. However, the development of drugs aiming at manipulating their proteolytic activity has been hampered by three major gaps in our knowledge of how they work in biological systems: 1) the elucidation of the molecular mechanisms behind substrate recognition and cleavage; 2) the regulation of their proteolytic activity, in particular at the epigenetic and post-translational level; 3) the integration of each protease into its network of substrates, inhibitors, cofactors and activators. Classic structure-function studies and system-wide approaches such as degradomics, that use a combination of genetics, epigenetics, cell biology, in vivo studies and proteomics, provide an invaluable contribution to our understanding of these different levels of biological complexity.

This Research Topic aims at providing a platform in which we can build a multi-level knowledge of the biological role of ADAMs, ADAMTSs and astacins. Examples of topics that are of interest include, but are not limited to:

• Structural studies
• Mechanistic aspects of proteolysis
• Methodologies to measure proteolytic activity in vitro, ex vivo and in vivo
• Regulation of proteolytic activity
• Elucidation of substrate repertoire
• In vivo studies
• System biology approaches to investigate the interactions between proteases, their substrates, inhibitors, cofactors and activators
• Therapeutic applications

Manuscripts, within the format of Frontiers, that will be considered include: Methods; Original Research; Opinion; Perspective; Brief Research Report; Review; Mini Review; Data Report; and Technology and Code. Please refer to this link for a full list of accepted article types including descriptions.

Professor Hang Fai Kwok has two filed patents on ADAM17 antibody applications in cancer and cardiovascular disease. All other Topic Editors declare no competing interests with regards to the Research Topic.

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