Abstract
Notch signaling orchestrates the regulation of cell proliferation, differentiation, migration and apoptosis of epidermal cells by strictly interacting with other cellular pathways. Any disruption of Notch signaling, either due to direct mutations or to an aberrant regulation of genes involved in the signaling route, might lead to both hyper- or hypo-activation of Notch signaling molecules and of target genes, ultimately inducing the onset of skin diseases. The mechanisms through which Notch contributes to the pathogenesis of skin diseases are multiple and still not fully understood. So far, Notch signaling alterations have been reported for five human skin diseases, suggesting the involvement of Notch in their pathogenesis: Hidradenitis Suppurativa, Dowling Degos Disease, Adams–Oliver Syndrome, Psoriasis and Atopic Dermatitis. In this review, we aim at describing the role of Notch signaling in the skin, particularly focusing on the principal consequences associated with its alterations in these five human skin diseases, in order to reorganize the current knowledge and to identify potential cellular mechanisms in common between these pathologies.
Highlights
Notch signaling is a ubiquitous and evolutionarily conserved intracellular pathway involved in the regulation of many diverse cellular functions and is implied in mediating responses that might be significantly variable and strictly linked to the activation context and the cellular type [1]
Canonical Notch signaling is triggered by the binding of Notch receptors to a DSL ligand exposed on a neighboring cell, which leads to a proteolytic processing of the membrane-bound receptor at cleavage sites located in the heterodimerization domain (HD) domain, referred to as site 2-4 (S2-4), to allow the release of an intracellular active fragment, the NICD
The released NICD active fragment might regulate transcription principally through two alternative mechanisms: the first contemplates the interaction of the active NICD with transcription factors not belonging to the CSL/RBP-Jκ family, including hypoxia-inducible factor (HIF) and monocyte enhancer factor-2 (Mef2) [44]; the second involves the delivery into the cytoplasm of a slightly different fragment from NICD resulting from the cleavage catalyzed by a distinct protease from presenilin of the γ-secretase complex [41,44]
Summary
Notch signaling is a ubiquitous and evolutionarily conserved intracellular pathway involved in the regulation of many diverse cellular functions and is implied in mediating responses that might be significantly variable and strictly linked to the activation context and the cellular type [1]. A deep characterization of Notch transduction is quite appealing since a progressively expanding spectrum of human diseases has been found to be associated with alterations in Notch signaling [3] These variations are either due to aberrant regulation or direct mutations leading to both hyper- or hypo-activation of the transcription of target genes or of the core components of the Notch signaling route [3]. We will describe the core components, key steps and principal modulators of Notch transduction to disclose the impact and consequences of their alterations in human skin diseases In this context, we intend to reorganize the current knowledge on the principle exerted functions of Notch pathway and to identify potential mechanisms in common between these diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
