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自身免疫性疾病:表观遗传学与治疗靶点的视角

Autoimmune disease: a view of epigenetics and therapeutic targeting.

机构信息

Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China.

出版信息

Front Immunol. 2024 Nov 13;15:1482728. doi: 10.3389/fimmu.2024.1482728. eCollection 2024.

Abstract

Autoimmune diseases comprise a large group of conditions characterized by a complex pathogenesis and significant heterogeneity in their clinical manifestations. Advances in sequencing technology have revealed that in addition to genetic susceptibility, various epigenetic mechanisms including DNA methylation and histone modification play critical roles in disease development. The emerging field of epigenetics has provided new perspectives on the pathogenesis and development of autoimmune diseases. Aberrant epigenetic modifications can be used as biomarkers for disease diagnosis and prognosis. Exploration of human epigenetic profiles revealed that patients with autoimmune diseases exhibit markedly altered DNA methylation profiles compared with healthy individuals. Targeted cutting-edge epigenetic therapies are emerging. For example, DNA methylation inhibitors can rectify methylation dysregulation and relieve patients. Histone deacetylase inhibitors such as vorinostat can affect chromatin accessibility and further regulate gene expression, and have been used in treating hematological malignancies. Epigenetic therapies have opened new avenues for the precise treatment of autoimmune diseases and offer new opportunities for improved therapeutic outcomes. Our review can aid in comprehensively elucidation of the mechanisms of autoimmune diseases and development of new targeted therapies that ultimately benefit patients with these conditions.

摘要

自身免疫性疾病包括一大类疾病,其发病机制复杂,临床表现具有显著异质性。测序技术的进步表明,除了遗传易感性外,各种表观遗传机制,包括 DNA 甲基化和组蛋白修饰,在疾病的发展中起着关键作用。新兴的表观遗传学领域为自身免疫性疾病的发病机制和发展提供了新的视角。异常的表观遗传修饰可以作为疾病诊断和预后的生物标志物。对人类表观遗传谱的探索表明,与健康个体相比,自身免疫性疾病患者的 DNA 甲基化谱明显改变。针对特定的表观遗传治疗方法正在不断涌现。例如,DNA 甲基化抑制剂可以纠正甲基化失调,缓解患者病情。组蛋白去乙酰化酶抑制剂(如伏立诺他)可以影响染色质的可及性,并进一步调节基因表达,已被用于治疗血液系统恶性肿瘤。表观遗传治疗为自身免疫性疾病的精准治疗开辟了新途径,为改善治疗效果提供了新的机会。我们的综述可以帮助全面阐明自身免疫性疾病的发病机制,并开发新的靶向治疗方法,最终使这些疾病的患者受益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/366e/11599216/ad20fb2a7884/fimmu-15-1482728-g001.jpg

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