The researchers have identified the gene HDAC2 and its associated protein and believe that they are promising targets for treating the disease. The gene regulates the expression of a number of genes involved in plasticity, the ability of the brain to change in response to the environment, and memory formation. It also seems to affect how other genes are expressed, affecting memory by decreasing the number of synapses and altering the structure of neural circuits.
For the study, the researchers bred mice with Alzheimer’s like symptoms, causing them to forget previously learned tasks and reducing their ability to learn new ones. They then treated them with histone deacetylase (HDAC) inhibitors, a class of 11 enzymes which regulate the expression of the gene. Following the treatment, the mice regained their long term memories and their ability to learn new tasks. Additionally, mice that were genetically engineered to not possess the gene showed enhanced memory function.
The enzymes act upon histones, the scaffold around which DNA is wound during chromosome formation. These histones undergo acetylation to change the shape structure of the chromatin. The enzymes inhibit deacetylation, and can open up the chromatin structure to enable the transcription of certain genes to take place that otherwise wouldn’t because the chromatin is packed too tightly.
The fact that long-term memory can be recovered by increasing histone acetylation perhaps shows that it just becomes inaccessible rather than lost in cases of memory loss.
References:
Guan, J. Haggarty, S. Giacometti, E. et al. (2009), "HDAC2 negatively regulates memory formation and synaptic plasticity." Nature 459: 55-60
Paddock, C. (2009) “Drugs That Target HDAC2 Gene Reversed Alzheimer's In Mice.”
