TY - JOUR
T1 - An overview of benefits and risks of chronic melanocortin-1 receptor activation
AU - Böhm, M.
AU - Robert, C.
AU - Malhotra, S.
AU - Clément, K.
AU - Farooqi, S.
N1 - Publisher Copyright:
© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α–melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals.
AB - The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α–melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals.
UR - http://www.scopus.com/inward/record.url?scp=85200045243&partnerID=8YFLogxK
U2 - 10.1111/jdv.20269
DO - 10.1111/jdv.20269
M3 - Review article
AN - SCOPUS:85200045243
SN - 0926-9959
JO - Journal of the European Academy of Dermatology and Venereology
JF - Journal of the European Academy of Dermatology and Venereology
ER -