Ghosh P, Saadat A
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). 2021 Mar 9. doi: 10.1016/j.nrl.2021.01.016.
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.
神经元功能和分化受到基因组和表观基因组的严格调控。基于环境信息，表观遗传变化会发生。神经退行性变是基因组和表观基因组失调的结果。在这项研究中，我们在不同神经退行性疾病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。包括染色质修饰、DNA甲基化和调节性RNA（miRNA）变化在内的表观遗传修饰，对神经退行性疾病以及记忆都有很大影响。这些在神经元细胞中的重新编辑效应会导致阿尔茨海默病、帕金森病、亨廷顿病，但在朊病毒病中观察到了一种不同寻常的神经表观遗传学形式。随后，为了开发这些疾病的治疗方法，应考虑表观遗传修饰。尽管到目前为止有许多关于药物发现的报道，抑制组蛋白脱乙酰酶和DNA甲基转移酶以逆转表观遗传变化，但它们缺乏靶向递送，有时还会对神经元细胞产生细胞毒性作用。未来，靶向性和非细胞毒性药物的进展应成为神经退行性疾病治疗的主要重点。
