Gene Involved in Neurodegeneration Keeps Clock Running

Northwestern University scientists have shown that a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock. In a study of the common fruit fly, the researchers found the gene, called Ataxin-2, keeps the clock responsible for sleeping and waking on a 24-hour rhythm. Without the gene, the rhythm of the fruit fly's sleep-wake cycle is disturbed, making waking up on a regular schedule difficult for the fly. The discovery is particularly interesting because mutations in the human Ataxin-2 gene are known to cause a rare disorder called spinocerebellar ataxia (SCA) and also contribute to amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. People with SCA suffer from sleep abnormalities before other symptoms of the disease appear. This study linking the Ataxin-2 gene with abnormalities in the sleep-wake cycle could help pinpoint what is causing these neurodegenerative diseases as well as provide a deeper understanding of the human sleep-wake cycle. The findings were published online on May 17. 2013 in Science. Ravi Allada, M.D., professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences, and Dr. Chunghun Lim, a postdoctoral fellow in his lab, are authors of the paper. Period (per) is a well-studied gene in fruit flies that encodes a protein, called PER, which regulates circadian rhythm. Drs. Allada and Lim discovered that Ataxin-2 helps activate translation of PER RNA into PER protein, a key step in making the circadian clock run properly. "It's possible that Ataxin-2's function as an activator of protein translation may be central to understanding how, when you mutate the gene and disrupt its function, it may be causing or contributing to diseases such as ALS or spinocerebellar ataxia," Dr. Allada said.