Epigenetics: a novel therapeutic approach for the treatment of Alzheimer's disease

Abstract

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.

Fig. 1. Epigenetic targets and therapeutic approaches for AD

DNA methylation and histone modification mediators involved in AD and potential therapeutic interventions under development reported in literature. Barrels = histones; (M) = methyl group; (Ac) = acetyl group. Abbreviations in the figure are as follows: DNMT, DNA methyltransferase; HAT, histone acetyltransferase; HDAC, histone deacetylase; SIRT, sirtuin.