A new mouse study has found that a hormone secreted during exercise reduces Parkinson’s disease symptoms.
Researchers from Johns Hopkins Medicine and the Dana Farber Cancer Institute in Boston have found that a hormone expelling into the blood during endurance or aerobic exercise reduces levels of a protein linked to common Parkinson’s disease symptoms.
Parkinson’s disease causes the brain to become progressively damaged over many years. The main symptoms include tremors, slow movement, and stiff, inflexible muscles. It is unknown what causes the loss of nerve cells which leads to Parkinson’s disease; however, the new findings published in Proceedings of the National Academy of Sciences could lead to exciting new developments.
Analysing irisin and its role in the body
Johns Hopkins Medicine’s Ted Dawson, MD, PhD, and Dana Farber’s Bruce Spiegelman, PhD joined forces to investigate the link between the exercise molecule irisin and Parkinson’s disease symptoms.
Research has already discovered a link between endurance exercise and Parkinson’s disease symptoms. Dawson, whose research has focused on neurodegenerative diseases, noted that the first clue to the link between exercise, Parkinson’s disease, and irisin came from Spiegelman, whose first paper addressing irisin was published in 2012.
The researchers tested the effects of irisin on Parkinson’s disease symptoms by using mouse brain cells that are engineered to spread small, spindly fibres of alpha-synuclein, a protein that regulates moods and movements related to the brain neurotransmitter dopamine.
When the alpha-synuclein proteins clump, those clusters kill dopamine-producing brain cells, a key trigger of Parkinson’s disease. These clumps are similar to what is found in the brains of people with Parkinson’s disease.
In the laboratory model, the researchers found that irisin prevented the clumps, therefore, mitigating brain cell death.
How does irisin affect Parkinson’s disease symptoms?
Once the team analysed irisin, they then tested irisin’s effects on mice engineered to have Parkinson’s disease symptoms. They injected alpha-synuclein into an area of the mouse brain where dopamine-producing neurons extend.
Two weeks later, the researchers injected a viral vector which increased irisin levels in the mice. The researchers discovered that after six months, the mice that received irisin had no muscle movement deficits, which is a common Parkinson’s disease symptom, whilst those injected with a placebo showed deficits in grip strength and their ability to descend a pole.
Further studies illuminated that the brain cells of the mice given irisin indicated that the exercise hormone reduced levels of Parkinson’s disease-related alpha-synuclein between 50% and 80%. Moreover, the researchers found that irisin speeds up the transport and degradation of alpha-synuclein via fluid-filled sacs called lysosomes in brain cells.
“If irisin’s utility pans out, we could envision it being developed into a gene or recombinant protein therapy,” said Dawson, referring to the widening field of drug development aimed at using cellular genetics to treat disease. Dawson is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases, professor of neurology and director of the Johns Hopkins Institute for Cell Engineering.
“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” added Spiegelman.
