遗传 ›› 2014, Vol. 36 ›› Issue (4): 295-300.doi: 10.3724/SP.J.1005.2014.0295

• 综述 •    下一篇

阿尔兹海默病中DNA甲基化对β-淀粉样蛋白的影响

邓钰双, 余刚   

  1. 重庆医科大学附属第一医院神经内科, 重庆400016
  • 收稿日期:2013-11-01 修回日期:2012-12-25 出版日期:2014-04-20 发布日期:2014-03-20
  • 通讯作者: 余刚, 硕士, 副教授, 研究方向:神经系统退行性疾病。E-mail: gangyuw2013@126.com E-mail:gangyuw2013@126.com
  • 作者简介:邓钰双, 硕士研究生, 专业方向:神经系统退行性疾病。E-mail: dyushuang@sina.com
  • 基金资助:

    重庆市自然科学基金项目(编号:2012JJA10044)资助

The effect of DNA methylation on β-amyloid accumulation in Alz-heimer’s disease

Yushuang Deng, Gang Yu   

  1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • Received:2013-11-01 Revised:2012-12-25 Online:2014-04-20 Published:2014-03-20

摘要:

DNA甲基化是最常见也是目前研究得最成熟的表观遗传机制, 近年来其在阿尔兹海默病(Alzheimer’s disease, AD)等神经系统退行性疾病中的作用逐渐受到研究者的关注。β-淀粉样蛋白(Beta-amyloid, Aβ)变性聚集与AD的主要病理特征——老年斑(Senile plaques, SP)的形成密切相关。同时, 它还能诱导细胞凋亡、激发炎症级联反应、产生氧化应激、导致线粒体功能障碍等, 从而加剧AD的病理过程。研究表明, DNA甲基化在Aβ生成、清除及毒性相关基因的调控中发挥着重要作用。由于DNA甲基化的可逆性, 深入探究DNA甲基化在AD发生、发展中的作用, 可能为AD的治疗带来曙光。文章综述了AD中DNA甲基化对Aβ的影响, 进一步阐释了AD发病的表观遗传学机制, 为AD的表观遗传学治疗提供了理论基础。

关键词: DNA甲基化, β-淀粉样蛋白, 阿尔兹海默病

Abstract:

DNA methylation is the most intensively studied mechanism for epigenetic gene regulation. The functions of DNA methylation have recently drawn wide attention for investigation into the etiology of neurodegenerative disorders such as Alzheimer’s disease (AD). It has been well established that β-amyloid (Aβ) accumulation leads to the formation of senile plaques, which is a hallmark of AD pathology. Aggregation of Aβ induces neurotoxicities manifested by apoptosis, neuroin-flammation, oxidative stress and mitochondrial dysfunction etc., which consequently provoke the pathological progression of AD. Previous studies have demonstrated that DNA methylation plays an important role in regulating genes associated with the production, clearance and aggregation of Aβ. DNA methylation is a reversible process, making it a promising target for AD therapeutics. Further studies of DNA methylation in the initiation and progression of AD would pave the road to explore improved approaches to treat this disease. In this review, we summarize the involvement of DNA methylation in Aβ accumulation as well as the associated pathological alterations during the initiation and progression of AD, which would help to fully appreciate the molecular basis of AD.

Key words: DNA methylation, beta-amyloid, Alzheimer’s disease (AD)