Genetic and environmental changes that disrupt the circadian rhythm, the body’s 24-hour internal clock that controls the sleep/wake cycle, may reduce the toxicity of a mutant gene for Huntington’s disease, a study in fruit flies found. The study could lead to new therapies for Huntington’s and other neurodegenerative diseases, the researchers suggest.
Researchers have long known that changes in the circadian clock that disrupt sleep and other activities are common among patients with neurodegenerative brain disorders such as Alzheimer’s, Parkinson’s, and Huntington’s. Scientists have observed that circadian or sleep disruption precedes the appearance of the diagnostic symptoms of the disease, suggesting that these features are impaired early in the disease process. But definitive evidence that the circadian clock can impact neurodegeneration in human disease models has been lacking, researchers say.
In the new study, researchers used a fruit fly model of Huntington’ disease. They disrupted the flies’ circadian clock, essentially giving them jet lag, to assess its effect on Huntington’s progression. They found that the “jet-lagged” flies had fewer toxic proteins linked to the disease and that fewer brain cells died. The researchers also found that silencing a gene that is controlled by the circadian clock and is involved in protein folding produced a similar effect.
The researchers suggest that their finding could lead to new approaches for preventing or slowing Huntington’s and other neurodegenerative diseases. Their study, partly funded by NHLBI, appears in Cell Reports.