Getting, Stephen J. and Kaneva, Magdalena and Bhadresa, Y. and Renshaw, Derek and Leoni , Giovanna and Patel, H.B. and Kerrigan, Mark J.P. and Locke, Ian C. (2009) Melanocortin peptide therapy for the treatment of arthritic pathologies. The Scientific World Journal, 9 . pp. 1394-1414. ISSN 1537-744X
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Official URL: http://dx.doi.org/10.1100/tsw.2009.163
Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC)-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [alpha-MSH]) and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1 to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed alpha-MSH) have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.
|Research Community:||University of Westminster > Life Sciences, School of|
|Deposited On:||20 Jan 2010 18:04|
|Last Modified:||20 Jan 2010 18:04|
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