Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
Neurologia (Engl Ed). 2023 Jul-Aug;38(6):e62-e68. doi: 10.1016/j.nrleng.2023.05.001.
Neuronal function and differentiation are tightly regulated by both genome and epigenome. Based on the environmental information the epigenetic changes occur. Neurodegeneration is the consequence of dysregulation of both the genome and epigenome. In this study, we saw different types of alterations of epigenome present in neuronal cells of different model organisms for neurodegenerative disorders. The epigenetic modifications including chromatin modification, DNA methylation, and changes in regulatory RNAs (miRNA) are having a great impact on neurodegenerative disorders as well as memory. The effects of these re-editing in the neuronal cells cause Alzheimer's disease, Parkinson's disease, Huntington's disease but an unusual form of neuroepigenetics has been seen in Prion Disease. Subsequently, for the development of treatment of these diseases, epigenetic modifications should be kept in mind. Although until now many reports came on drug discovery inhibiting histone deacetylases and DNA methyltransferases to reverse the epigenetic change but they lack targeted delivery and sometimes cause a cytotoxic effect on neuronal cells. In future, advancement in targeted and non-cytotoxic drugs should be the main focus for therapeutic treatment of the neurodegenerative disorders.
神经元的功能和分化受到基因组和表观基因组的严格调控。根据环境信息，表观遗传变化发生。基因组和表观基因组的失调是神经退行性疾病的结果。在这项研究中，我们在神经退行性疾病不同模型生物的神经元细胞中观察到了不同类型的表观基因组改变。表观遗传修饰包括染色质修饰、DNA 甲基化和调节 RNA（miRNA）的变化，对神经退行性疾病以及记忆都有很大的影响。这些在神经元细胞中的重新编辑会导致阿尔茨海默病、帕金森病、亨廷顿病，但朊病毒病中出现了一种异常形式的神经表观遗传学。随后，为了开发这些疾病的治疗方法，应该考虑表观遗传修饰。尽管到目前为止，已经有很多关于发现抑制组蛋白去乙酰化酶和 DNA 甲基转移酶以逆转表观遗传变化的药物的报告，但它们缺乏靶向递送，有时会对神经元细胞产生细胞毒性作用。在未来，靶向和非细胞毒性药物的进展应该是神经退行性疾病治疗的主要重点。
