Exercise Hormone May Help Find A Cure For Parkinson’s

Symptoms of PD typically will develop slowly and worsen over time. They can include tremors. Impaired balance and coordination, changes in gait, fatigue, loss of smell, mood changes, depression, changes in nerves that control facial muscles, and sleep problems. Currently, there may be no effective treatments or cures, but there are some medications, occupational therapy, and research that suggest that exercise can help to alleviate symptoms and improve quality of life. 

Studies also suggest that many of the symptoms of Parkinson’s disease may be due to the alpha-synuclein clumps accumulating in the brain that can lead to cell death. A recent study published in PNAS has now found that a hormone that is produced during aerobic exercise can help to prevent the formation of these cell-killing clumps. 

According to Dr. Katherine Fletcher who is a Research Communication Manager at Parkinson’s UK, “The results of this study are significant because, although we know that physical activity and exercise are beneficial for people with Parkinson’s, it’s currently unclear how this impacts the cells and processes in the brain that are contributing to symptoms of the condition. This study sheds some light on how a hormone produced during exercise might be acting to protect vital brain cells from dying in Parkinson’s.”

Previous studies have shown that exercise may help to improve cognitive function and benefit those with PD or Alzheimer’s disease. Irisin, a molecule that is secreted into the blood during endurance exercise, has been identified in recent research as possibly contributing to this benefit. 

Researchers set out to investigate these beneficial effects of irisin secretion further they created a mouse model of Parkinson’s disease as the molecule is secreted in the same way in both humans and mice. The mice brain cells were engineered to produce fibers of alpha-synuclein proteins that form clumps as is found in the brains of people with PD, and these clumps kill dopamine-producing neurons. 

Irisin was administered to these nerve cells in vitro, results revealed that after administration the alpha-synuclein fibers did not form clumps, and the irisin molecules also prevented the brain cells from dying, according to the researchers. After the success of the in vitro experiments, the team of researchers moved on to investigations in live mice that were engineered to have Parkinson's-like symptoms. 

Alpa-synuclein was injected in the striatum area of the mouse brains which has many dopamine-producing neurons, then after two weeks, irisin molecules were injected into the tail veins of the mice. 

The researchers found that after 6 months any mice that did not receive the irisin injection developed muscle impairment, displayed reduced grip strength, and were less able to descend a pole. However, the mice that were injected with irisin were found to have no muscle movement deficits. 

Further investigation revealed that the irisin injections had crossed the blood-brain barrier and blocked the formation of alpha-synuclein clumps. Additionally, the irisin injection was found to have had no effect on alpha-synuclein monomers that are thought to be important in transmitting nerve impulses. 

Brain tissue analysis showed that alpha-synuclein clumps in the treated group of mice were up to 80% reduced when compared to the mice that were given placeboes. This effect was found to be due to lysosomal degradation of the alpha-synuclein clumps which the findings suggest were promoted by the irisin injections. 

According to the researchers, “Our demonstration that irisin reduces pathologic α-syn is particularly relevant to the pathogenesis of PD and related α-synucleinopathies since pathologic α-syn appears to be the major pathogenic driver of these disorders.”

“Given that irisin is a naturally produced peptide hormone and seems to have evolved to cross the blood-brain barrier, we think it is worth continuing to evaluate irisin as a potential therapy for Parkinson’s and other forms of neurodegeneration,” states corresponding author Dr. Bruce Spiegelman, Ph.D. of the Dana-Farber Cancer Institute.

Dr. Fletcher notes that although this study was in mice, this molecule is also secreted in humans by their muscle and skeletal tissues during exercise, however, exercise alone may not be able to produce sufficient quantities of the molecule to have the same effects that were displayed in this study. “It’s unclear from these results if exercise alone would generate enough irisin to have protective effects or if using other means to boost this hormone might be a more realistic therapeutic option in the future.”

The fact that the irisin injections were able to cross the blood-brain barrier to reach the alpha-synuclein clumps suggests the potential as a future treatment for Parkinson’s disease after more research. The researchers believe that these very early findings are an optimistic step in the positive direction towards a potentially effective treatment. 

“There is considerable promise that it might be developed as a disease-modifying therapy for the treatment of PD. […] It will be important for any future human therapy to determine whether irisin can arrest the progression of experimental PD after neurological symptoms have started and to determine the effects of irisin in other PD models.”

“The research has so far been done in a lab-based setting and will need further development before paving the way for a future therapy that might be able to slow or stop the condition for people with Parkinson’s,” said Dr. Fletcher who goes on to add, “Anything that shows promise in protecting brain cells in Parkinson’s offers hope, as currently there are no treatments that can slow or stop the condition.”