Department of Pharmacology, Vallabhbhai Patel Chest Institute, Faculty of Medicine, University of Delhi, Delhi 110007, India.
Rev Neurosci. 2018 Mar 28;29(3):241-260. doi: 10.1515/revneuro-2017-0049.
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders mainly affecting elderly people. It is characterized by progressive loss of memory and cognitive function. More than 95% of AD cases are related to sporadic or late-onset AD (LOAD). The etiology of LOAD is still unclear. It has been reported that environmental factors and epigenetic alterations play a significant role in AD pathogenesis. Furthermore, recently, genome-wide association studies (GWAS) identified 10 novel risk genes: ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, MS4A6A, MS4A4E, and PICALM, which play an important role for LOAD. In this review, the therapeutic approaches of AD by epigenetic modifications have been discussed. Nowadays, HDAC inhibitors have clinically proven its activity for epigenetic modifications. Furthermore, we try to establish the relationship between HDAC inhibitors and above mentioned LOAD risk genes. Finally, we are hoping that this review may open new area of research for AD treatment.
阿尔茨海默病（AD）是最常见的神经退行性疾病之一，主要影响老年人。其特征是进行性记忆和认知功能丧失。超过 95%的 AD 病例与散发性或迟发性 AD（LOAD）有关。LOAD 的病因仍不清楚。据报道，环境因素和表观遗传改变在 AD 发病机制中起重要作用。此外，最近，全基因组关联研究（GWAS）确定了 10 个新的风险基因：ABCA7、APOE、BIN1、CD2AP、CD33、CLU、CR1、MS4A6A、MS4A4E 和 PICALM，它们对 LOAD 起重要作用。在这篇综述中，讨论了通过表观遗传修饰治疗 AD 的方法。目前，HDAC 抑制剂已在临床上证明其对表观遗传修饰的活性。此外，我们试图建立 HDAC 抑制剂与上述 LOAD 风险基因之间的关系。最后，我们希望这篇综述能为 AD 的治疗开辟新的研究领域。
