HDAC1 Activators Improve DNA Repair in Neurons to Treat Cognitive Decline

HDAC1 is involved in a form of DNA repair, but levels decline with age, as well as in Alzheimer's disease. This leads to a greater accumulation of unrepaired oxidative DNA damage in neurons. Researchers here note that increased activation of HDAC1 appears to improve cognitive function via a reduction in this oxidative DNA damage. An HDAC1 activator drug has been tested as a treatment for dementia, but caused serious side-effects. Better compounds or other approaches may be able to obtain similar benefits without the harms. There are several members of the HDAC family of enzymes, and their primary function is to modify histones - proteins around which DNA is spooled. These modifications control gene expression by blocking genes in certain stretches of DNA from being copied into RNA. In 2013, researchers linked HDAC1 to DNA repair in neurons. In the current paper, the researchers explored what happens when HDAC1-mediated repair fails to occur. To do that, they engineered mice in which they could knock out HDAC1 specifically in neurons and another type of brain cells called astrocytes. For the first several months of the mice's lives, there were no discernable differences in their DNA damage levels or behavior, compared to normal mice. However, as the mice aged, differences became more apparent. DNA damage began to accumulate in the HDAC1-deficient mice, and they also lost some of their ability to modulate synaptic plasticity - changes in the strength of the con...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs