Matrix metalloproteinases and A disintegrin and metalloproteinases (MMPs and ADAMs) (MMPs and ADAMs)

Matrix metalloproteinases (MMPs) and A Disintegrin and Metalloproteinases (ADAMs) are two families of zinc-dependent endopeptidases that are essential for the modification of the extracellular environment and the regulation of cell-surface protein signaling. MMPs, also known as matrixins, primarily function to degrade and remodel various components of the extracellular matrix (ECM), such as collagen, elastin, and fibronectin, which is critical for physiological processes like wound healing, bone development, and angiogenesis (Source: PubMed, PMID: 28273522). ADAMs, or adamalysins, are transmembrane proteins that facilitate 'ectodomain shedding,' the process of releasing the extracellular portions of membrane-bound proteins, including cytokines like TNF-alpha and growth factors like TGF-alpha, thereby modulating diverse signaling pathways (Source: UniProt, P78536). In disease states, the overactivity of these enzymes is linked to cancer metastasis, where they promote tumor invasion, as well as chronic inflammatory conditions and cardiovascular diseases (Source: NIH, 'Matrix Metalloproteinases in Health and Disease'). While they represent significant therapeutic targets, the clinical development of broad-spectrum inhibitors has been hindered by severe side effects, most notably musculoskeletal syndrome (MSS), which causes debilitating joint pain and stiffness (Source: Nature Reviews Drug Discovery, doi:10.1038/nrd745). Consequently, current research focuses on the development of highly selective inhibitors that can target specific disease-associated isoforms while sparing those necessary for normal tissue homeostasis.

Other names

MatrixinsAdamalysinsMetalloproteinasesMMP familyADAM familyZinc-dependent metalloproteinases

Inhibition of the zinc-dependent catalytic domain to prevent the proteolytic cleavage of extracellular matrix components or the shedding of cell-surface signaling molecules (Source: PubMed, PMID: 12069711).