The first men on the moon almost didn’t make it home – all because of a stuck switch.
While heading out for a moonwalk, Buzz Aldrin accidentally bumped the control panel, breaking off a switch. No just any switch, either. It was a very important switch, specifically the one that that powered the engines – the very engines they were relying on to get them back home. The switch was now stuck. If they didn’t fix it, they would die on the moon sitting atop a rocket that couldn’t be ignited.
With ingenuity that would make MacGuyver proud, the astronauts found a solution. They able to restore functioning to the stuck switch – using a felt-tipped pen.
Now scientists have discovered the genetic ‘stuck switch’ is behind Rett syndrome. And these molecular MacGuyvers have even figured out a way to restore functioning to the affected systems.
Rett syndrome, an autism-like condition, is caused by mutations in the gene MECP2 (methyl CpG binding protein 2). The protein MECP2 is present in the nucleus where is involved in switching other genes on or off (via the process of DNA methylation.)
One of the genes regulated by MECP2 is the Cloride potassium supporter (KCC2) which is found in neurons. Scientists took cells from patients with Rett’s, turned them into stem cells, and then turned those stem cells into neurons. Unlike control neurons, the neurons from patients with Rett’s exhibited a lack of KCC2. This lack of KCC2 delays the switch of the neurotransmitter GABA from having an excitatory role to an inhibitory role.
In this study, overexpression of KCC2 restored the GABA functioning. Researchers used insulin-like growth factor 1 (IGF1) which increased the levels of KCC2, thus restoring GABA function. This leads the authors to speculate that “restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome.”
This piece of the puzzle brought to you by: “KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome“