Alzheimer’s Disease: the Potential of Epigenetic Treatments and Current Clinical Candidates

Abstract

Alzheimer’s disease is a progressive and fatal neurodegenerative disease affecting 50 million people worldwide, characterized by memory loss and neuronal degeneration. Current treatments have limited efficacy and there is no cure. Alzheimer's is likely caused by a combination of factors, providing several potential therapeutic targets. One area of interest is the epigenetic regulation of gene expression within the brain. Epigenetic marks, including DNA methylation and histone modifications, show consistent changes with age and in those with Alzheimer’s. Some epigenetic regulation has been linked to disease pathology and progression and are the focus of current research. Epigenetic regulators might make promising therapeutic targets yet challenges need to be overcome to generate an efficacious drug lacking deleterious side effects.

Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview

“… 140 These compounds have shown some promise in the studies of AD since they appear to reduce AD pathology in vitro and memory impairments in vivo. 141 …”

“… 144 It has been observed that increased HDAC2 and HDAC3 activity exerts a negative impact on cognition, while reduced HDAC1 activity may be neurotoxic; therefore, HDAC-based therapy inhibiting HDAC2 or HDAC3, but not HDAC1 could represent potential therapeutic target for AD. 141 For instance, RGFP-966, a selective HDAC3 inhibitor has been shown to decrease pathological tau phosphorylation and Aβ protein expression, improve learning and memory and normalize a number of AD-related genes in cellular and animal AD model. 145 Other examples of specific HDACi are tubacin, a selective HDAC6 inhibitor, and suramin, a selective S1RT1 and S1RT2 inhibitor.…”

“…Therefore, only partial histone methyltransferase inhibition could help restore balanced enzyme function. 141 In summary, despite substantial progress, the role of histone epigenetic modifications in AD and their potential for AD treatment require further investigation. In the future, obtained pharmacoepigenetic data could help to optimize the precision medicine approach to AD.…”

Protection Induced By Ginsenoside Rb1 in Alzheimer’s Disease Model is Associated With Redressing The Neuronal Hyperexcitability Which is Regulated By Nav1.2 and Nav1.6

“…The NOR task is last for three days and all mice were placed in a transparent plastic box with size of 40×40×40 cm 3 . The rst day was used as a habituation phase, while the second day was used as exploratory phase and last day was used for testing.…”

“…Alzheimer's disease (AD) is the main reason of dementia in elderly individuals, which is characterized by progressive memory loss and cognitive impairment [1,2]. AD is a widespread disease that has affected more than 50 million people, and there is currently no effective cure for it [3]. Thus, it is urgent to nd an effective medicine for AD.…”