Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, QC, H3G 1Y6, Canada.
Clin Rev Allergy Immunol. 2010 Aug;39(1):62-77. doi: 10.1007/s12016-009-8172-8.
Several lines of evidence suggest the involvement of disturbance in epigenetic processes in autoimmune disease. Most noteworthy is the global DNA hypomethylation seen in lupus. Epigenetic states in difference from genetic lesions are potentially reversible and hence candidates for pharmacological intervention. Potential targets for drug development are histone modification and DNA methylating and demethylating enzymes. The most advanced set of drugs in clinical development are histone deacetylase (HDAC) inhibitors. However, the prevalence of DNA hypomethylation in lupus suggests that we should shift our attention from HDAC inhibitors to DNA demethylation inhibitors. MBD2 was recently proposed to be involved in demethylation in T cells in lupus and is, therefore, a candidate target. Although this field is at its infancy, it carries great promise.
有几条证据表明，自身免疫性疾病涉及到表观遗传过程的紊乱。最值得注意的是狼疮中观察到的全基因组 DNA 低甲基化。与遗传损伤不同，表观遗传状态是潜在可逆的，因此是药物干预的候选者。药物开发的潜在靶点是组蛋白修饰和 DNA 甲基化和去甲基化酶。在临床开发中最先进的一组药物是组蛋白去乙酰化酶 (HDAC) 抑制剂。然而，狼疮中 DNA 低甲基化的普遍性表明，我们应该将注意力从 HDAC 抑制剂转移到 DNA 去甲基化抑制剂上。MBD2 最近被提出参与狼疮 T 细胞中的去甲基化，因此是一个候选靶点。尽管该领域还处于起步阶段，但它具有很大的前景。
