Epigenetic regulation in Alzheimer's disease: is it a potential therapeutic target?

Abstract

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. Changes in DNA methylation and post-translational modifications of histone tails are increasingly observed in AD tissues, and likely contribute to disease onset and progression. The reversibility of these epigenetic marks offers the potential for therapeutic interventions.Areas covered: After a concise and updated overview of DNA methylation and post-translational modifications of histone tails in AD tissues, this review provides an overview of the animal and cell culture studies investigating the potential of targeting these modifications to attenuate AD-like features. PubMed was searched for relevant literature between 2003 and 2021.Expert opinion: Methyl donor compounds and drugs acting on histone tail modifications attenuated the AD-like features and improved cognition in several transgenic AD mice; however, there are concerns about safety and tolerability for long-term treatment in humans. The challenges will be to take advantage of recent epigenome-wide investigations to identify the principal targets for future interventions, and to design novel, selective and safer agents. Natural compounds exerting epigenetic properties could represent a promising opportunity to delay disease onset in middle-aged individuals at increased AD risk.

Keywords: Alzheimer’s disease; DNA methylation; S-adenosylmethionine; animal models; epigenetic drugs; epigenetic therapy; epigenetics; histone tail modifications; inhibitors of DNA methyltransferases (DNMTi).