Study of ‘sticky’ gene sheds light on how certain sedatives work

Researchers are reporting that Valium and other benzodiazepines—sedatives used to treat anxiety, sleeping disorders, and other conditions—appear to work by a previously unknown mechanism. The discovery of this mechanism sheds light on how these sedatives work in the body and could lead to the design of more effective treatments for a variety of neurological and neuropsychiatric disorders, they say.   

Between 1999 and 2017, the United States experienced a 10-fold increase in the number of people who died from overdoses of Valium and other benzodiazepines. For years, scientists believed that these sedatives worked alone to calm nerves.  In lab studies using mouse nerve cells, the researchers showed that these drugs do not work alone in their action on the nerves but appear to need the assistance of a ‘sticky’ gene called Shisa7, which produces a protein that gets stuck to nerve receptors called GABA type A receptors.  This protein appeared to make the receptors more sensitive to sedatives. Experiments in live mice supported the findings. Mice that lacked the Shisa7 gene, for example, were much less likely to fall asleep than normal mice that were given high levels of sedatives.

The study, which appeared in Science, was partly supported by the NHLBI.