表观遗传修饰在阿尔兹海默病中的研究进展

Research progress of epigenetics in Alzheimer's disease

表观遗传是指在不改变基因序列的情况下,通过对基因进行可逆性修饰改变基因表达。阿尔兹海默病(Alzheimer’s disease,AD)是一种最常见的神经退行性疾病,表现为进行性记忆缺失、脑萎缩、脑内形成淀粉样斑块和神经纤维缠结。表观遗传学修饰在AD的发生发展中具有重要作用。综述了DNA甲基化、组蛋白乙酰化、microRNA等表观遗传修饰对AD中的记忆缺失、APP水解、Aβ淀粉样斑块形成、Tau蛋白磷酸化、氧化应激等现象的影响及其机制。

Epigenetics refers to heritable changes in gene expression, caused by modifications which do not involve alterations in DNA sequence. Alzheimer＇s disease （AD） is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and brain atrophy. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neuro-fibrillary tangles, along with extracellular accumulations of amyloid [3 protein （A~）, called senile plaques, are known to be the neuropathological hallmarks of AD. Recent studies have suggested that epigenetic mechanisms may play a pivotal role in AD course and development. In this review, we summarize recent advances on change of memory loss, APP hydrolysis, AI3 protein formation, tau protein phosphorylation, oxidative stress caused by common epigenetic modifications （DNA methylation, histone modifications, microRNA）.