Gangisetty Omkaram, Murugan Sengottuvelan
Endocrine Research Facility, Department of Animal Sciences, Rutgers University, 67 Poultry Farm Lane, New Brunswick, NJ, 08901, USA.
Hematology/Oncology Division, Perelman School of Medicine, University of Pennsylvania, Clinical Research Building, Philadelphia, 19104, PA, USA.
Adv Neurobiol. 2016;12:1-25. doi: 10.1007/978-3-319-28383-8_1.
Epigenetic modifications, including DNA methylation, covalent histone modifications, and small noncoding RNAs, play a key role in regulating the gene expression. This regulatory mechanism is important in cellular differentiation and development. Recent advances in the field of epigenetics extended the role of epigenetic mechanisms in controlling key biological processes such as genome imprinting and X-chromosome inactivation. Aberrant epigenetic modifications are associated with the development of many diseases. The role of epigenetic modifications in various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington disease, epilepsy, and multiple sclerosis is rapidly emerging. The use of epigenetic modifying drugs to treat these diseases has been the interest in recent years. A number of natural products having diverse mechanism of action are used for drug discovery. For many years, natural compounds have been used to treat various neurodegenerative diseases, but the use of such compounds as epigenetic modulators to reverse or treat neurological diseases are not well studied. In this chapter, we mainly focus on how various epigenetic modifications play a key role in neurodegenerative diseases, their mechanism of action, and how it acts as a potential therapeutic target for epigenetic drugs to treat these diseases will be discussed.
表观遗传修饰,包括DNA甲基化、组蛋白共价修饰和小非编码RNA,在调节基因表达中起关键作用。这种调节机制在细胞分化和发育中很重要。表观遗传学领域的最新进展扩展了表观遗传机制在控制关键生物学过程(如基因组印记和X染色体失活)中的作用。异常的表观遗传修饰与许多疾病的发生有关。表观遗传修饰在包括阿尔茨海默病、帕金森病、亨廷顿病、癫痫和多发性硬化症在内的各种神经退行性疾病中的作用正在迅速显现。近年来,使用表观遗传修饰药物治疗这些疾病受到了关注。许多具有不同作用机制的天然产物被用于药物研发。多年来,天然化合物一直被用于治疗各种神经退行性疾病,但将此类化合物用作表观遗传调节剂来逆转或治疗神经疾病的研究并不充分。在本章中,我们主要关注各种表观遗传修饰如何在神经退行性疾病中起关键作用、它们的作用机制,以及其作为表观遗传药物治疗这些疾病的潜在治疗靶点将如何发挥作用。