Washington, August 29: Researchers have claimed that problems with a key group of enzymes called topoisomerases could have profound effects on the genetic machinery behind development of brain and potentially lead to autism spectrum disorder (ASD).
Senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at University of North Carolina School of Medicine, said that 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.
He said that this could point to an environmental component to autism.
Zylka said that a temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development.
This study could also 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 overwound, a common occurrence that can interfere with key biological processes.
Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs.
Zylka and his colleagues stumbled upon the discovery by accident 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.
Of the more than 300 genes that are linked to autism, nearly 50 were suppressed by topotecan. Suppressing that many genes across the board-even to a small extent-means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene.
The research has been published in the journal Nature. (ANI)