Exifone Reverses DNA Damage in Mice Suffering From Dementia and Alzheimer's in MIT Study

Researchers from the Massachusetts Institute of Technology (MIT) recently made an immense discovery that the HDAC1 enzyme plays a vital role in the repair of age-related DNA damage to genes associated with various cognitive functions and memory. Neurologists have shown that people living with Alzheimer’s disease can highly benefit from this suggested medication.

A Woman With Alzheimer

The neurologists who used mice for their research proved that when the HDAC1 enzyme is lost, some DNA damage accumulates as the mice age. The most exciting part of this study is that these researchers discovered that this specific damage could be reversed to enhance cognitive function. Evidence shows that this can be accomplished by using a drug that will act as an activator for HDAC1.

The HDAC enzyme family has several members whose main work is to transform the proteins around which DNA is bound (histones). These modifications precisely control gene expression by blocking the copy of genes in individual segments of DNA in RNA.

The HDAC1 enzyme research

Observation showed that during the first few months, no discernible difference in the levels of DNA damage as compared to the normal mice. However, the difference became more evident as the mice aged. DNA damage started to build up in HDAC1-deficient mice, and they also lost some of their synaptic plasticity modulation ability. There were also alterations in space navigation assessment and memory in older mice lacking HDAC1.

The study revealed that deficiency of HDAC1 caused a condition called oxo-guanine DNA damage of 8, signifying damage of oxidative DNA.

8-oxo-guanine DNA damage can, however, be repaired by an enzyme called OGG1, and the study reveals that the HDAC1 enzyme can activate OCG1. In cases where there is HDAC1 deficiency, OCG1 fails to activate, leaving the damage unrepaired. The researchers discovered several genes that are more likely to suffer this type of damage are important to the function of synapses.

Target neurodegeneration

Several years ago, the authors of this new study, Tsai and Stephen Haggarty studied groups of tiny molecules seeking to establish potential drug compounds that could inhibit and activate members of the HDAC family. One of the drugs chosen was exifone; a drug approved in the 80s in Europe to treat dementia. In the current release research paper, Tsai and Pao have used exifone to see if it has the potential to reverse the age-related DNA damage, exhibited by mice with HDAC1 deficiency.

The researchers used exifone on two groups of mice: a group of healthy old mice and another with Alzheimer’s. The drug boosted the cognitive abilities and memory of both groups of mice. In all cases, they found that the drug lowered levels of oxidative DNA damage in the brain and improved the cognitive functions of mice, including memory.

Tsai says she is optimistic that other safe HDAC1-activating drugs may be worth pursuing as potential treatments for age-related cognitive decline and Alzheimer’s disease.