ADAMTS proteinases: potential therapeutic targets?
ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases have been implicated in a number of connective tissue pathologies including Ehlers-Danlos syndrome type VII C, Weill-Marchesani syndrome, encephalomyelitis, and arthritis. These proteinases therefore represent potential therapeutic targets for the treatment of such conditions. The synthesis and activity of ADAMTS proteinases is regulated at multiple levels: transcription, RNA splicing, translation, proteolytic processing, cofactor stimulation and inhibition, each of which represents a possible point of therapeutic intervention. Recent research suggests that, in addition to the direct inhibition of ADAMTS proteinases with low molecular weight non-peptidic inhibitors, targeting the transcription and protein processing of these enzymes could be effective therapeutic approaches.
Rheumatology Research Unit, Level E6 (Box 194), Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. gjj23@cam.ac.uk
Gavin C
GC
Jones
D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D003240:Connective Tissue Diseases / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
D011480:Protease Inhibitors; D051722:ADAM Proteins