Emerging Roles of Post-Translational Modifications in Skin Diseases: Current Knowledge, Challenges and Future Perspectives

Abstract

Post-translational modifications (PTMs) of proteins represent as a key step in regulating their biological functions and dynamic interaction with other players. This process is fine-tuned by a myriad of enzymes named “writers, readers and erasers” whose actions are precisely controlled. Either the mutation, aberration in the expression of the aforementioned enzymes or their substrates have shown to participate in the pathogenesis of various skin diseases such as melanoma, vitiligo, psoriasis, eczema, atopic dermatitis and inherited dermatological diseases. It is becoming increasingly clear that key transcriptional factors, inflammation-related molecules are prone to PTMs. Despite their importance in regulating key processes including inflammation, keratinocyte apoptosis, proliferation and differentiation, PTMs have received less attention due to the challenges involved. Here in this review we summarize the role of the most common types and the newly discovered PTMs, including acetylation, glycosylation, citrullination, PARylation and sumoylation in dermatoses and surveys the recent progress in PTM-based therapeutic approaches in skin diseases.

Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects

“…They also underly the importance of SIRTs and PARPs regarding their therapeutic application in skin diseases. SIRTs and PARP inhibitors or activators could be a new biological drug in psoriasis development [111]. However, some effort must be taken to design inhibitors and activators specific to one target.…”

Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance

“…Notably, AD ranks 15th among the largest nonfatal disease burdens worldwide, while its pathogenesis is multifactorial and unclear in most affected individuals ( Laughter et al, 2021 ; Ständer, 2021 ). Moreover, PTMs show therapeutic potential for curbing inflammation and restoring barriers, which are closely linked to numerous skin and autoimmune disorders ( Yang and Yan, 2022 ). Exploring the indexes of PTMs therefore yield novel therapeutic targets, predictive events, monitor trends, or prognostic indicators for the clinical outcomes of AD patients.…”