Crystal ball gazing: new therapeutic targets for hyperuricaemia and gout.
Recent studies in diverse disciplines have led to significant advances in the understanding of the basic biology of hyperuricaemia and gout, with important implications for future treatment. These findings include genetic variation within SLC2A9 as a key regulator of urate homeostasis, and identification of urate-anion exchanger urate transporter 1 (URAT1) and other renal uric acid transporters. Recognition of urate as an endogenous danger signal and activator of the adaptive immune response suggests an important role for urate crystals in non-microbial immune surveillance. The central role of NALP3 inflammasome activation and IL-1beta signalling in the initiation of the acute gout attack raises the possibility of new therapeutic targets. Disordered osteoclastogenesis in patients with chronic gout highlights potential therapies for prevention of joint damage. This review summarizes these findings and the potential relevance for future management of gout.
Dalbeth
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Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Private Bag 92019, Auckland, New Zealand. n.dalbeth@auckland.ac.nz
Merriman
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D001862:Bone Resorption / Q000209:etiology; D003460:Crystallization; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006073:Gout / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006074:Gout Suppressants / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic; D014527:Uric Acid / Q000378:metabolism
D051246:Glucose Transport Proteins, Facilitative; D006074:Gout Suppressants; C411811:SLC2A9 protein, human; D014527:Uric Acid