The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances

银屑病 发病机制 表观遗传学 后生 计算生物学 医学 生物信息学 生物 皮肤病科 遗传学 免疫学 DNA甲基化 基因 基因表达
作者
Saeed Aslani,Seyed Mohamad Javad Mirarefin,Habib Zarredar,Milad Asadi,Mohammad Javan,Arezou Khosrojerdi,Thomas P. Johnston,Amirhossein Sahebkar
出处
期刊:Current Medicinal Chemistry [Bentham Science]
卷期号:31 (29): 4621-4639 被引量:1
标识
DOI:10.2174/0929867330666230503143824
摘要

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.
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