Epigenetic mechanisms involving the modulation of gene activity without modifying the DNA bases are reported to have lifelong effects on mature neurons in addition to their impact on synaptic plasticity and cognition. Histone methylation and acetylation are involved in synchronizing gene expression and protein function in neuronal cells. Studies have demonstrated in experimental models of neurodegenerative disorders that manipulations of these two mechanisms influence the susceptibility of neurons to degeneration and apoptosis. In Alzheimer’s disease (AD), the expression of presenilin 1 (PSEN1) is markedly increased due to decreased methylation at CpG sites, thus promoting the accumulation of toxic amyloid-β (Aβ) peptide. In Parkinson’s disease (PD), dysregulation of α-synuclein (SNCA) expression is presumed to occur via aberrant methylation at CpG sites, which controls the activation or suppression of protein expression. Mutant Huntingtin (mtHTT) alters the activity of histone acetyltransferases (HATs), causing the dysregulation of transcription observed in most Huntington’s disease (HD) cases. Folate, vitamin B6, vitamin B12, and S-adenosylmethionine (SAM) are vital cofactors involved in DNA methylation modification; 5-azacytidine (AZA) is the most widely studied DNA methyltransferase (DNMT) inhibitor, and dietary polyphenols are DNMT inhibitors in vitro. Drug intervention is believed to reverse the epigenetic mechanisms to serve as a regulator in neuronal diseases. Nevertheless, the biochemical effect of the drugs on brain function and the underlying mechanisms are not well understood. This review focuses on further discussion of therapeutic targets, emphasizing the potential role of epigenetic factors including histone and DNA modifications in the diseases.

据报道，涉及在不修改 DNA 碱基的情况下调节基因活性的表观遗传机制除了对突触可塑性和认知的影响外，还会对成熟神经元产生终身影响。组蛋白甲基化和乙酰化参与同步神经元细胞中的基因表达和蛋白质功能。研究已经在神经退行性疾病的实验模型中证明，对这两种机制的操纵会影响神经元对退化和细胞凋亡的敏感性。在阿尔茨海默病 (AD) 中，由于 CpG 位点甲基化减少，早老素 1 (PSEN1) 的表达显着增加，从而促进有毒淀粉样蛋白-β (Aβ) 肽的积累。在帕金森病 (PD) 中，推测 α-突触核蛋白 (SNCA) 表达的失调是通过 CpG 位点的异常甲基化发生的，该位点控制蛋白质表达的激活或抑制。突变亨廷顿蛋白 (mtHTT) 改变组蛋白乙酰转移酶 (HAT) 的活性，导致在大多数亨廷顿病 (HD) 病例中观察到的转录失调。叶酸、维生素 B6、维生素 B12 和S-腺苷甲硫氨酸 (SAM) 是参与 DNA 甲基化修饰的重要辅助因子；5-氮杂胞苷（AZA）是研究最广泛的DNA甲基转移酶（DNMT）抑制剂，膳食多酚是体外DNMT抑制剂。药物干预被认为可以逆转表观遗传机制，作为神经元疾病的调节剂。然而，药物对脑功能的生化作用及其潜在机制尚不清楚。本综述侧重于进一步讨论治疗靶点，强调包括组蛋白和 DNA 修饰在内的表观遗传因素在疾病中的潜在作用。