Neuronal approach for pigmentary spots

At the same time, a better understanding of the role played by cellular stress in the formation of these spots enables the neutralisation of pigment overproduction in these localised areas. This original course of action is translated by significant results on the reduction in size and pigmentation of these brown spots. Pigmentary spots are characteristics of older skin and photo-exposed epidermis, which in both cases are combined with a high cellular stress rate. The brown colour of these spots is due to a localised overproduction of melanin. The pigment synthesis process is the same in the case of tanning as in the case of pigmentary spots; it is the intrinsic factors that regulate this pigmentation which differ, either in their expressed quantity or in their origin. Skin pigmentation depends on cellular interactions between keratinocytes and melanocytes. Exposure to UV stimulates the transcription of the gene called POMC (pro-opio-melano-cortin complex) coding for the hormone ?-MSH (alphamelanocyte stimulating hormone), ACTH (adreno corticotrophic hormone) as well as beta-endorphin. Recent observations by the team of Dr Fisher1 highlighted the regions of genomic DNA involved in the regulation of the POMC gene transcription. These analyses have revealed a functional regulating DNA sequence, target of the tumour suppressing protein p53. The work also shows that the transcription of POMC (and therefore the regulation of ?-MSH) is dependent on the stabilisation of p53 after a genotoxic stress and that it is quantitatively much more significant in keratinocytes than in melanocytes.2 The implications of this discovery directly concerns the understanding of the formation of pigmentary spots. According to Dr Fisher, pigmentary spots result from a group of cells producing pigments in response to repeated stress of the skin. However, p53 is classically defined as the stress protein, expressed consecutively to intense cellular stress situations.1 Via an activation of p53, the stressed skin keratinocytes would therefore increase the basal rate of POMC (and therefore of ?-MSH), at the origin of pigmentary spot formation. In parallel, a study on the innervations of the epidermis has shown a correlation between the degree of epidermal enervation and photo-chronic damage.3 Thus, skin suffering from accelerated photoageing would present a highly innervated epidermis. However, neuronal factors are included among the intrinsic factors able to regulate skin pigmentation. In fact, neurons and melanocytes are both derived from the same cells of the neural crest. The neuropeptides therefore have stimulating effects on the melanocytes.4 In their study, Hara M et al5 have shown a physical connection between the ends of intra-epidermal axons and melanocytes. This connection would function on a synaptic mode. The nerve ending delivers a neuropeptide that fixes a receptor on the surface of the melanocyte. Among the most represented neuropeptides at epidermal level, there is in particular CGRP, which has been shown to stimulate the number of melanocytes, and substance P of which the receptor TaqR1 is located on the surface of the dendrites of melanocytes. The work presented here by Codif International describes the role of substance P in the stimulation of melanogenesis by dendritic melanocytes, then secondly the effect of a sea lily extract: Neurolight.61 G (now referred to as ‘the sea lily extract’) acting both on the substance P pathway and on the regulation of POMC, thus permitting an innovative and original solution for the treatment of pigmentary spots.

Materials and methods

Effect of substance P on melanogenesis