MSH peptides and applications to treatment of hair

Abstract

The proopiomelanocortin (POMC) system is an evolutionary conserved regulatory module representing one of the best characterized neuropeptide networks which can be considered as an equivalent of the hypothalamic-pituitary-adrenal axis. POMC contains within its structure the amino acid sequences of several hormonal products (ACTH, alpha-melanocyte-stimulating hormone (aMSH), ßMSH, and yMSH, the endogenous opioids α -, β- and γ-endorphin). While originally identified as regulators of pigmentation, the POMC system is responsible for the balance of several physiologic processes. One of the most important players of the melanocortin (MC) system is aMSH, a neuro immunomodulatory peptide. In addition to its pigmentary capabilities, aMSH has been addressed as potent anti-inflammatory protein downregulating proinflammatory cytokines. AMSH can be detected in: Melanocytes, monocytes, B cells, natural killers, a subset of cytotoxic T cells, epithelial cells and in keratinocytes. The MCs mediate their biological effects by binding to five different MC receptors (MC-Rs) belonging to the superfamily of G protein-coupled receptors. Distibution of each MC-Rs varies among the different tissues, cell type and during cell differentiation. The hair follicle is a typical stress-responding mini organ with a peculiar immune system in which the human follicle bulge meets all key criteria of an immunoprivileged tissue site. This immune privilege is characterized primarily by a low expression of major histocompatibility (MHC) class I antigens. Moreover, the anagen hair bulb lacks a lymphatic system and almost devoid of intraepithelial T cells. Indeed, anagen hair bulbs locally generate potent immunosuppressants. Thereafter immune privilege collapse may favor autoimmune disease development like alopecia areata. Due to its anti-inflammatory and immunomodulatory activity and to its highly favorable safety profile, aMSH has already been exploited as a promising candidate for immune privilege restoration in several immune diseases. In addition to αMSH, follicular cells produce other POMC-derived peptides such as ACTH and β-endorphin; those molecules, as well as αMSH and its related peptides, k(D)PT and KPV, may assist in the maintenance or restoration of the unique immune system of the hair follicle and could be eventually considered as potential therapeutic agents for immune hair disorders.