ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS4)

ADAM metallopeptidase with thrombospondin type 1 motif 4 (commonly abbreviated as ADAMTS4, also known as Aggrecanase-1) is a secreted metalloproteinase enzyme belonging to the ADAMTS protein family[1][3][2]. It has a modular structure, including a metalloproteinase domain, a disintegrin-like domain, and a single thrombospondin type 1 (TS) motif. ADAMTS4 is primarily recognized for its ability to degrade key components of the extracellular matrix, most notably aggrecan, the major cartilage proteoglycan, as well as brevican, neurocan, and versican[1][3]. This proteolytic activity is upregulated in osteoarthritis and contributes to cartilage breakdown[1][3]. ADAMTS4 is also expressed in nervous tissue and may play roles in neurodegeneration, as well as in tumor progression (e.g., glioma)[1][3]. Its physiological activity is regulated by endogenous inhibitors such as TIMP3, and its dysregulation is implicated in diseases marked by abnormal extracellular matrix remodeling[1][3][6]. Therapeutic targeting of ADAMTS4 is being explored for degenerative joint diseases, but inhibition must be carefully balanced to avoid disrupting normal tissue structure and repair[1][3].

Other names

Aggrecanase-1ADAMTS-4ADMP-1KIAA0688

Inhibition of aggrecanase activity to block proteoglycan degradation in cartilage Modulation of extracellular matrix composition through protease inhibition