ADAMTS4

ADAMTS4, also known as aggrecanase-1, is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of zinc-dependent metalloproteinases. The ADAMTS family is involved in cleaving extracellular matrix components, processing pro-proteins, and inhibiting angiogenesis.

ADAMTS4 specifically cleaves aggrecan, a major component of cartilage. This cleavage contributes to the degradation of cartilage matrix in conditions such as osteoarthritis and rheumatoid arthritis. The enzyme cleaves aggrecan between the Glu373 and Ala374 residues within the interglobular domain, generating specific fragments that can be detected and used as biomarkers for cartilage degradation.

ADAMTS4 is synthesized as a proenzyme, which requires activation to become catalytically active. The regulation of ADAMTS4 activity is complex and involves transcriptional control, post-translational modifications, and interactions with other molecules in the extracellular environment.

Research on ADAMTS4 has focused on its role in arthritis and other diseases involving cartilage degradation. It is considered a potential therapeutic target for the treatment of these conditions. Inhibitors of ADAMTS4 are being investigated as potential disease-modifying osteoarthritis drugs (DMOADs). Beyond arthritis, ADAMTS4 has also been implicated in other biological processes, including neuronal development and synaptic plasticity.