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.
Jones
Gavin C
GC
Rheumatology Research Unit, Level E6 (Box 194), Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. gjj23@cam.ac.uk
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