Mao Qiao, Luo Zhixiong, Wang Kesheng, Chen Bin, Wang Zhiren, Zhang Yong, Wang Xiaoping, Luo Xingguang
Department of Psychosomatic Medicine, People's Hospital of Deyang City, Deyang, Sichuan 618000, China.
College of Integrative Medicine, Fujian University of Traditional Medicine, Fuzhou 350122, China.
SciBase Neurol. 2024;2(2). Epub 2024 Jul 22.
This study investigates the role of histone tail modifications in Parkinson's disease (PD), emphasizing the epigenetic regulation of genes associated with the disease. PD primarily manifests in individuals over 60, suggesting that PD-causal genes remain dormant until later in life, influenced by environmental factors and epigenetic modifications. Histone modifications such as methylation, acetylation, phosphorylation, and ubiquitylation play crucial roles in gene expression regulation by altering chromatin structure or interacting with gene regulatory regions. Specifically, modifications on histones H2A, H2AX, H3, and H4 have been linked to PD. For instance, α-synuclein (α-SYN) aggregation, a hallmark of PD, is regulated by histone modifications like H3K27ac and H3K4me3, which enhance α-SYN expression and contribute to PD progression. Conversely, repressive marks like H3K9ac and H3K27me3 can mitigate PD risk by reducing α-SYN levels. Therapeutic strategies targeting these histone modifications, such as the use of GSK-J4 or vitamin C-treated neural stem cells, show potential in alleviating PD symptoms by modulating histone marks and gene expression. Understanding these epigenetic mechanisms offers promising avenues for developing novel treatments for PD.
本研究调查了组蛋白尾部修饰在帕金森病（PD）中的作用，着重于与该疾病相关基因的表观遗传调控。PD主要在60岁以上的个体中表现出来，这表明导致PD的基因在生命后期才会被激活，受到环境因素和表观遗传修饰的影响。甲基化、乙酰化、磷酸化和泛素化等组蛋白修饰通过改变染色质结构或与基因调控区域相互作用，在基因表达调控中发挥关键作用。具体而言，组蛋白H2A、H2AX、H3和H4上的修饰与PD有关。例如，α-突触核蛋白（α-SYN）聚集是PD的一个标志，它受H3K27ac和H3K4me3等组蛋白修饰的调控，这些修饰增强了α-SYN的表达并促进了PD的进展。相反，H3K9ac和H3K27me3等抑制性标记可以通过降低α-SYN水平来降低PD风险。针对这些组蛋白修饰的治疗策略，如使用GSK-J4或维生素C处理的神经干细胞，通过调节组蛋白标记和基因表达，在减轻PD症状方面显示出潜力。了解这些表观遗传机制为开发治疗PD的新方法提供了有前景的途径。
