Inhibiting enzyme HDAC2 may help prevent neurodegeneration

Researchers have restored some cognitive function in mouse models with Alzheimer’s disease by genetically blocking the enzyme HDAC2. Results of the study from a team at the Massachusetts Institute of Technology suggest drugs that inhibit HDAC2 may be suitable for the treatment of neurodegenerative disease.

In a previous study, the researchers used a strain of mutant mice that had profound neuron and synapses loss. The mice also carried the amyloid-beta plaques thought to cause Alzheimer’s disease and showed impaired learning and memory. When the mice were given drugs that block all 19 known HDAC enzymes, they gained more synapses and demonstrated improved memory function. A later study demonstrated that one of the 19 HDAC enzymes, HDAC2, caused synapse and memory loss in normal mice.

In the current study, researchers used both of these findings to investigate HDAC2s in the mutant mice. An elevated level of the HDAC2 was found in both the hippocampus and the entorhinal cortex regions of the brain. The researchers also reported that HDAC2 binds to memory genes in these brain regions, thereby dampening the gene expressions.

To silence the HDAC2 enzyme in neurons in the hippocampus region researchers used a technique called RNA interference. The result was a dramatic increase in synaptic plasticity. Additionally, mutant mice were indistinguishable from normal controls following the administration of two different memory tests.

Though blocking HDAC2 expression did not change the number of dying neurons, according to the researchers, the findings suggest that memory can be improved even in later stages of the disease.

Disclosures: The researchers report no relevant financial disclosures.