Exercise Hormone Reduces Parkinson’s Disease-Associated Brain Degeneration and Symptoms in Animal Model

An exercise-related hormone, irisin, administered to animals with a model of Parkinson’s disease reduced nerve degeneration and symptoms associated with the progressive movement disorder, say scientists from Dana-Farber and Johns Hopkins Medicine. About one million people in the United States, and 10 million people worldwide are living with Parkinson’s, which is characterized by tremors, slowed muscular movements, and impaired balance and coordination. About 60,000 new cases of Parkinson’s are diagnosed in the United States each year.

Administering irisin to rodents that had been engineered to develop brain lesions associated with Parkinson’s disease prevented the accumulation of a toxic protein that kills dopamine-producing brain cells, which are essential for control of body movements, the scientists report in the Aug. 31 issue of Proceedings of the National Academy of Sciences. Treatment with irisin also prevented the loss of muscle movement abilities, such as grip strength and the ability to descend a pole.

The researchers, led by Bruce Spiegelman, PhD, of Dana-Farber and Ted Dawson, MD, PhD, of Johns Hopkins Medicines, say that the study provides evidence that irisin, which is released by muscles during endurance exercise, can reach the brain and halt or reverse some of the deficits found in Parkinson’s disease. Spiegelman discovered irisin in 2012, and he and other scientists have proposed that the production of irisin by muscular activity is responsible for a variety of benefits of exercise, including improved cognitive function and bone health.

“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,” says Spiegelman.

The disease predominately affects the dopamine-producing neurons in an area of the brain called the substantia nigra. There currently is no standard therapy for Parkinson’s. Medications are available that may improve symptoms but none that effectively slow or stop the underlying disease.

Dawson, who is the director of the Johns Hopkins Institute for Cell Engineering, and Spiegelman tested the effects of irisin using mice whose brain cells had been engineered to spread fibers of alpha synuclein, a protein that regulates moods and movements related to the brain neurotransmitter dopamine. When alpha synuclein proteins form clumps, they kill dopamine-producing brain cells – a key trigger of Parkinson’s disease. Fibrous clumps of alpha synuclein are similar to what is found in the brains of people with Parkinson’s. In the laboratory model, irisin prevented the accumulation of alpha synuclein clumps and brain cell death.

Mice given irisin had levels of Parkinson’s disease-related alpha synuclein that were 50% to 80% lower than those with the Parkinson’s model that did not receive irisin.

Much research needs to be done to determine if there are human therapeutic implications of these findings. “We could envision it being developed into a gene or recombinant protein therapy,” says Dawson.

Other Dana-Farber researchers involved in the irisin study were Jonathan G. Van Vranken, PhD; Melanie Mittenbühler, PhD; Hyeonwoo Kim, PhD, and Mu A, PhD.

About the Medical Reviewer

Dr. Spiegelman received his PhD in biochemistry from Princeton University in 1978, and completed postdoctoral work at Massachusetts Institute of Technology. In 1982, he joined DFCI and was promoted to professor in 1991. His research focuses on cell differentiation, cellular metabolism, and genetic factors involved in obesity and diabetes.