Department of Preclinical and Clinical Pharmacology, Viale Pieraccini 6, University of Florence, 50139 Florence, Italy.
Trends Mol Med. 2012 Feb;18(2):92-100. doi: 10.1016/j.molmed.2011.10.002. Epub 2011 Nov 9.
Despite significant advancement in developing therapies for multiple sclerosis (MS), drugs that cure this devastating disorder are an unmet need. Among the remedies showing efficacy in preclinical MS models, inhibitors of poly(ADP-ribose) polymerase (PARP)-1 have gained great momentum. Emerging evidence demonstrates that PARP-1 inhibitors epigenetically regulate gene expression and finely tune transcriptional activation in immune and neural cells. In this review, we present an appraisal of the effects of PARP-1 and its inhibitors on immune activation, with particular emphasis on the processes taking place during the autoimmune attack directed against the central nervous system. One explanation is that drugs inhibiting PARP-1 activity protect from neuroinflammation in MS models via immunomodulation and direct neuroprotection. PARP-1 inhibitors have already reached the clinical arena as cancer treatments, and observations made in treating these patients could help advance treatments for MS.
尽管在开发多发性硬化症（MS）的疗法方面取得了重大进展，但治愈这种毁灭性疾病的药物仍未得到满足。在临床前 MS 模型中显示出疗效的治疗方法中，聚（ADP-核糖）聚合酶（PARP）-1 的抑制剂备受关注。新出现的证据表明，PARP-1 抑制剂通过表观遗传调控免疫和神经细胞中的基因表达，并精细调节转录激活。在这篇综述中，我们评估了 PARP-1 及其抑制剂对免疫激活的影响，特别强调了针对中枢神经系统的自身免疫攻击过程中发生的情况。一种解释是，抑制 PARP-1 活性的药物通过免疫调节和直接神经保护来防止 MS 模型中的神经炎症。PARP-1 抑制剂已经作为癌症治疗药物进入临床领域，对这些患者进行的观察可能有助于推进 MS 的治疗方法。
