The research to date has been conducted using fruit flies, looking at Huntington’s disease. The researchers, from Northwestern University, found that Huntington’s disease-related neurodegeneration improved in a fruit fly model after the flies experienced a life cycle of jet lag. The reason for using fruit flies – the classic model organism for scientific research – was because the neurons that govern flies’ sleep-wake cycles are very similar to those of people.
Huntington’s disease is an inherited disorder that results in death of brain cells. The disease is a type of condition that stops parts of the brain working properly over time. The symptoms begin with alterations to mood or mental abilities, followed by a lack of coordination and an unsteady gait often follow.
Further examination showed that jet lag protected neurons from damage, which was pinpointed to a Huntington’s disease protein (called Heat Shock Protein 70/90 Organizing Protein (Hop)). This was revealed after the scientists shut off the clock-controlled gene.
A circadian rhythm refers to any biological process that displays an endogenous, entrainable oscillation of about 24 hours. These 24-hour rhythms are driven by a circadian clock, and they are common to plants and animals. It has been observed in patients with neurodegenerative diseases that they often experience disruption to their circadian rhythms, to the extent that significant disruptions to the sleep-wake cycle are among the early indicators of neurodegenerative diseases.
The researchers disrupted the flies’ circadian rhythms. In one set, they altered the flies’ environment by changing the daily timing of light-dark cycles. With a second set of flies, the researchers mutated a gene that associated with control of the circadian clock. In essence, the researchers created continual jet-lag. With both groups, mutant Huntington’s disease proteins aggregated less and fewer neurons died.
Commenting on the research, lead scientist Dr. Ravi Allada states: “It seems counterintuitive, but we showed that a little bit of stress is good. We subtly manipulated the circadian clock, and that stress appears to be neuroprotective.”
The overall conclusion was that there is a link between circadian rhythms and neurodegenerative diseases. The significance could be towards alternate treatment pathways which could one day slow the progression of neurodegenerative diseases. Further study will be undertaken, and the researchers are keen to assess the effects on Alzheimer’s disease.
The research has been published in the journal Cell Reports. The research paper is titled “Circadian clocks function in concert with heat shock organizing protein to modulate mutant Huntingtin aggregation and toxicity.”
