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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances

Author(s): Saeed Aslani, Seyed Mohamad Javad Mirarefin, Habib Zarredar, Milad Asadi, Mohammad Reza Javan, Arezou Khosrojerdi*, Thomas P. Johnston and Amirhossein Sahebkar*

Volume 31, Issue 29, 2024

Published on: 03 July, 2023

Page: [4621 - 4639] Pages: 19

DOI: 10.2174/0929867330666230503143824

Price: $65

Abstract

Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis. A complex interplay between environmental factors and genetic risk factors has been suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of psoriasis between monozygotic twins and environmental factors that contribute to its onset have caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation, and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is characterized by heritable alterations in the transcription of genes without nucleotide change and is commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs. To date, scientific evidence has indicated abnormal DNA methylation, histone modifications, and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect the major enzymes involved in the methylation of DNA, or the acetylation of histones, which aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review, we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and discuss future challenges.

Keywords: Psoriasis, autoimmunity, epigenetics, DNA methylation, histone modifications, non-coding RNA.

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