A hurricane, a car accident, a roadside bomb, a rape — extreme stress is more common than you might think, with an estimated 50 to 60 percent of Americans experiencing it at some point in their lives. About 8 percent of that group will be diagnosed with post-traumatic stress disorder, or PTSD. They will have flashbacks and nightmares. They will feel amped up, with nerves on a permanent state of high alert. They won’t be able to forget.
Long-lasting memories require specific gene expression programmes that are, in part, orchestrated by epigenetic mechanisms. Of the epigenetic modifications identified in cognitive processes, histone acetylation has spurred considerable interest. Whereas increments in histone acetylation have consistently been shown to favour learning and memory, a lack thereof has been causally implicated in cognitive impairments in neurodevelopmental disorders, neurodegeneration and ageing. As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.
Neuroscientists show that HDAC2 enzyme could be a good target for new drugs.
MIT neuroscientists have shown that an enzyme overproduced in the brains of Alzheimer’s patients creates a blockade that shuts off genes necessary to form new memories. Furthermore, by inhibiting that enzyme in mice, the researchers were able to reverse Alzheimer’s symptoms.
The finding suggests that drugs targeting the enzyme, known as HDAC2, could be a promising new approach to treating the disease, which affects 5.4 million Americans. The number of Alzheimer’s victims worldwide is expected to double every 20 years, and President Barack Obama recently set a target date of 2025 to find an effective treatment.
Li-Huei Tsai, leader of the research team, says that HDAC2 inhibitors could help achieve that goal, though it would likely take at least 10 years to develop and test such drugs.