Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
Pharmacol Ther. 2013 Jul;139(1):41-50. doi: 10.1016/j.pharmthera.2013.03.010. Epub 2013 Apr 3.
Alzheimer's disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to the lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field.
阿尔茨海默病(AD)是老年人中最常见的痴呆症类型。其特征是脑内两种形式的聚集物沉积,即淀粉样β斑块和 tau 神经原纤维缠结。目前,尚无用于治疗 AD 的疾病修饰剂获得批准。已批准的药物疗法针对的是外周症状,但不能预防或减缓疾病的进展。尽管有几种疾病修饰性免疫治疗药物正在临床开发中,但由于缺乏疗效或严重的不良反应,许多药物都失败了。表观遗传变化,包括 DNA 甲基化和组蛋白修饰,参与学习和记忆,最近因其作为 AD 治疗潜在靶点的潜力而备受关注。动态和潜在的表观遗传改变被纳入 AD 的病理途径,为 AD 和其他神经退行性疾病提供了有价值的、可逆转的治疗靶点。表观遗传药物治疗癌症的获批为其他疾病(包括神经退行性疾病)的表观遗传药物的开发开辟了道路。特别是,甲基供体和组蛋白去乙酰化酶抑制剂正在被研究,以寻找可能的治疗效果,以挽救此类疾病中发现的记忆和认知能力下降。这篇综述探讨了表观遗传学在 AD 干预中的潜在应用,并介绍了该领域的最新发现。
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