Harnessing neuroendocrine controls of keratin expression: A new therapeutic strategy for skin diseases?

Abstract

Human skin produces numerous neurohormones and neuropeptides. Recent evidence has shown that the neuroendocrine regulation of human skin biology also extends to keratins, the major structural components of epithelial cells. For example, thyrotropin-releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1-ligands profoundly modulate human keratin gene and protein expression in human epidermis and/or hair follicle epithelium in situ. Since selected keratins are now understood to exert important regulatory functions beyond mechanical stability, we argue that neuroendocrine pathways of keratin regulation are important for maintaining skin and hair follicle homeostasis. This invites innovative neuroendocrine therapeutic interventions for skin disorders characterized by abnormal keratin expression, ranging from psoriasis to genodermatoses, and for promoting skin wound healing and hair growth. This strategy can be probed in simple, but instructive and readily available human skin and hair follicle organ culture assays as ideal models for exploring this new neuroendocrine frontier in translational epithelial biology.

The twisting tale of woolly hair: a trait with many causes

“…They allow structural stability to the cell and via interaction with desmosomes to the whole tissue 31 32. Recently, it was revealed that keratins may serve many more functions than only structural stability, and specific keratins influence protein synthesis, cytokine secretion and keratinocyte migration.…”

“…It is now well known that keratin expression can be modulated by external factors, such as hormones,31 32 sulforaphane81 or sirolimus 82. However, it would probably be extremely difficult to target such modulators directly to the IRS.…”

Cover Image: Neuroendocrine treatment of inherited keratin disorders by cannabinoids?

“…The available treatment options for this debilitating condition, such as retinoids, are highly unsatisfactory and associated with severe adverse effects . A promising novel approach for the treatment of keratin disorders may be to upregulate the expression of compensatory keratins and/or to downregulate the expression of the mutated keratins by neuroendocrine mediators that profoundly modulate the expression of selected keratins . The current illustration underscores the potential of this as yet untapped, innovative treatment strategy for inherited human keratin disorders.…”

Keratins: the hair shaft's backbone revealed

“…). These two keratins are expressed in the same anatomical region of the hair shaft, in the mid‐cortex . Later on, a single case of monilethrix was reported to be caused by a mutation in KRT83 , which is also expressed in the mid‐cortex of the hair shaft ; however, since this report in 2005, no additional K83‐related cases have been described.…”