Translational Cancer Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital, James's Street, Dublin 8, Ireland.
Clin Epigenetics. 2011 Aug;2(2):257-77. doi: 10.1007/s13148-011-0025-7. Epub 2011 Feb 18.
Huntington's disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD.
亨廷顿病(HD)是一种使人虚弱的神经退行性疾病,给患者和医疗保健成本都带来了巨大负担。尽管进行了广泛的研究,但此类患者的治疗选择仍然有限。蛋白质异常的翻译后修饰(PTM)正成为 HD 发病机制中的一个重要因素。这些 PTM 包括乙酰化、磷酸化、甲基化、SUMO 化和泛素化。有几类蛋白质参与调节这些 PTM。在这篇综述中,我讨论了将异常 PTM 与异常调节这些 PTM 的细胞机制联系起来与 HD 发病机制相关的现有证据。最后,我讨论了有证据表明,通过药理学靶向这些蛋白家族之一组蛋白去乙酰化酶,可能对 HD 的治疗具有潜在的治疗益处。