Mutations in the gene encoding Aprataxin are the second leading cause of an early onset hereditary ataxia termed ataxia-oculomotor apraxia 1. Early onset ataxias are progressive, neurological disorders, with the patients losing balance and motor coordination in their hands and legs, and suffering from other symptoms such as controlling ocular movements.
"As with many diseases for which genes were identified by positional cloning, one begins with insufficient information about the encoded protein that would allow one to formulate a disease hypothesis, let alone develop potential therapeutic strategies," said lead author Dr. Charles Brenner, associate professor of genetics and of biochemistry at Dartmouth Medical School. "By identifying an enzymatic activity of Aprataxin, we were able to formulate the disease hypothesis that Aprataxin activity on protein substrates in the developing brain is required for normal neurological development."
By establishing that Aprataxin has an enzymatic activity, Brenner said, researchers can focus attention on potential Aprataxin target proteins that might be regulated by this gene. "Though we don't think we can reverse the disease by putting the Aprataxin gene back in, we think we might be able to improve the functions of target proteins once we understand their roles and the consequences of their regulation by Aprataxin. In this way, the enzymatic activity of Aprataxin takes us to Aprataxin target proteins and potential therapeutic strategi
Contact: Andy Nordhoff
Dartmouth Medical School