Current and emerging treatments targeting the neuroendocrine system for disorders of the skin and its appendages.

The skin as a neuroendocrine organ and the role of neuroendocrine signaling in the development of disorders affecting the skin and its appendages has received increasing attention in the last years. Different neuroendocrine systems have been described in the barrier organ skin, including the thyroid system, the hypothalamic-pituitary-adrenal axis, the opioid, the endocannabinoid, the cholinergic, the secosteroidogenic and the serotonergic systems. All of these systems have been implicated in the development of skin diseases, which often have an inflammatory origin. These discoveries have led to an increase in the development of new drugs targeting components of neuroendocrine signaling pathways. Additionally, attempts have been made to repurpose already approved drugs targeting neuroendocrine signaling pathways in other organs for the treatment of skin diseases. Recently published results from preclinical and clinical studies look promising and may offer improved therapies to patients suffering from skin diseases in the near future. In this review, from a pharmaceutical point of view, we focus on recent progress in synthetic drug development of compounds targeting neuroendocrine signaling in the skin and its appendages to treat skin diseases such as atopic dermatitis, psoriasis, acne, alopecia areata and hyperhidrosis.