Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), researchers said. (Agencies)
Scientists at the University of North Carolina School of Medicine have described a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder's genetic causes.
"Our study shows the magnitude of what can happen if topoisomerases are impaired," said senior study author Mark Zylka, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC.
"Inhibiting these enzymes has the potential to profoundly affect neurodevelopment - perhaps even more so than having a mutation in any one of the genes that have been linked to autism," said Zylka.
The study could have important implications for ASD detection and prevention. Also, it could explain why some people with mutations in topoisomerases develop autism and other neurodevelopmental disorders.
Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes over wound, a common occurrence that can interfere with key biological processes.
Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells.
"If there are additional compounds like this in the environment, then it becomes important to identify them," said Zylka.
"That's really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects - so that pregnant women can avoid being exposed to these compounds," Zylka said.
Zylka and his colleagues stumbled upon the discovery while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy.
Investigating the drug's effects in mouse and human-derived nerve cells, they noticed that the drug tended to interfere with the proper functioning of genes that were exceptionally long - composed of many DNA base pairs.
The group then made the serendipitous connection that many autism-linked genes are extremely long.
"That's when we had the 'Eureka moment'. We realized that a lot of the genes that were suppressed were incredibly long autism genes," said Zylka.
Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), researchers said.