Neuropeptides and skin disorders. The new frontiers of neuro–endocrine–cutaneous immunology

Abstract

In the past, much work has been devoted to psychosomatic dermatology (or psychodermatology) by well-known pioneers. In recent years, the molecular mechanism by which neuropeptides (NPs) link the neural-immune-endocrine axis has been receiving increasing attention. This bidirectional communication between the immune-endocrine system and the nervous system also involves soluble factors, such as neurotransmitters and cytokines, that are produced by each system. It is also well known that the skin contains numerous NPs released from the sensory nerves and produced by the resident cells of the immune system or by skin cells. Functional dysregulation of NPs has been associated with pathologic cutaneous conditions, such as psoriasis and atopic dermatitis, and the current understanding of the bidirectional loops between the immune-endocrine system and the central and autonomic nervous systems may clarify the pathophysiology of these diseases, thus providing potential targets for therapeutic interventions. General concepts 1-3NPs are a heterogeneous group of molecules consisting of two or more of the 40 amino acids that are present in the central and peripheral nervous systems, where they act as neurotransmitters and/or neuromodulators producing specific biological activities. Several studies have demonstrated, in particular for substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP), NP synthesis and release by different cells in the skin and by a subpopulation of small unmyelinated afferent neurons (C fibers or C polymodal nociceptors) and small myelinated Aδ fibers localized in human dermis and epidermis. NPs act as neurotransmitters of the afferent system and are responsible, as neuromodulators, for neurogenic

The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris

“…11,12 Activation of the hypothalamic-pituitary-adrenal (HPA) axis with release of stress neuropeptides (NP) is essential for biological homeostasis and responses to external and internal challenges. 13,14 It has been confirmed that facial skin from acne patients is characterized by increased numbers of substance P-containing nerves and mast cells, and by strong expression of neutral endopeptidase in SG compared with normal skin. 15 SG expresses receptors for β-endorphin, corticotrophin-releasing factor (CRH), urocortin, propiomelanocortin, vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide.…”

“…By means of their autocrine, paracrine and endocrine actions, these neuroendocrine factors appear to mediate centrally and topically induced stress towards the SG, ultimately affecting the clinical course of acne. [12][13][14][15][16][17][18] CRH, its binding protein (CRHBP) and CRH receptors (CRHR) act as a central regulatory system of the HPA axis. 19 CRH is a 41-amino acid polypeptide.…”

Dermatological and immunological conditions due to nerve lesions

“…They are contained in and released from a wide range of nerves. Chemically distinct, neuropeptides exhibit characteristic patterns of localization within the PNS and CNS and, acting as neurotransmitters and/or neuromodulators, possess the ability to stimulate a range of diverse biological activities (Lotti et al, 1999). The concept of co-transmission within the ANS was first advanced by Burnstock (1976).…”

Psoriasis and Stress – Psoriasis Aspect of Psychoneuroendocrinology

“…Lipids are synthesized in the keratinocytes during epidermal differentiation and are then extruded into the extracellular domains, where they form lipid-enriched extracellular layers (Jensen et al, 2009). Activation of HPA axis with release of stress neuropeptides is essential for biological homeostasis and responses to external and internal challenges (Lotti et al, 1999) (bSlominski et al, 1996.…”