Melanocortin peptide therapy for the treatment of arthritic pathologies

TY - JOUR

T1 - Melanocortin peptide therapy for the treatment of arthritic pathologies

AU - Getting, S J

AU - Kaneva, M

AU - Bhadresa, Y

AU - Renshaw, D

AU - Leoni, Giovanna

AU - Patel, H B

AU - Kerrigan, M J P

AU - Locke, I C

PY - 2009/12/16

Y1 - 2009/12/16

N2 - 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.

AB - 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.

KW - Animals

KW - Arthritis/drug therapy

KW - Arthritis, Gouty/drug therapy

KW - Arthritis, Rheumatoid/drug therapy

KW - Humans

KW - Inflammation/drug therapy

KW - Melanocortins/therapeutic use

KW - Osteoarthritis/drug therapy

KW - Receptors, Melanocortin/drug effects

KW - Signal Transduction/drug effects

U2 - 10.1100/tsw.2009.163

DO - 10.1100/tsw.2009.163

M3 - Review article

C2 - 20024514

SN - 1537-744X

VL - 9

SP - 1394

EP - 1414

JO - TheScientificWorldJournal

JF - TheScientificWorldJournal

ER -