Exercise has so many benefits and is so necessary for active and healthy aging that doctors prescribe it as another therapy to prevent and alleviate the symptoms of many diseases. New research has now shown that irisina hormone released into the blood by skeletal muscle and other tissues while you exercise aerobic exercise or resistance exercisereduces levels of a protein linked to Parkinson’s disease – toxic alpha-synuclein – and stop them parkinsonian symptoms in mice.
If this finding is confirmed in new studies and clinical trials, it may serve as a basis for using irisin as a therapeutic molecule against Parkinson’s and other neurodegenerative diseases. The research was conducted by scientists from Johns Hopkins Medicine and the Dana Farber Cancer Institute in Boston (USA) on mice that had been modified to have symptoms similar to those caused by Parkinson’s disease, and their results were published in Proceedings of the National Academy of Sciences (PNAS).
Use of irisin for the treatment of neurodegenerative diseases
It has long been known that Endurance exercise relieves Parkinson’s symptoms and in 2012 Dr. Bruce Spiegelman of Dana Farber published an article on irisin in Nature and other scientific journals in which he noted that a protein called irisin peptide is released into the blood and increases with resistance exercise. Over the past 10 years, several labs have discovered this exercise increases blood levels of irisinwhich sparked interest in studying the relationship between this hormone and neurodegenerative pathologies such as Alzheimer’s or Parkinson’s disease.
Mice given irisin had no muscle movement deficits, but those given a placebo showed deficits in grip strength and in their ability to climb down a pole
Spiegelman and Dr. Ted Dawson, professor of neuroscience and director of the Johns Hopkins Institute for Cellular Engineering, decided to investigate the relationship between this exercise hormone and Parkinson’s disease and began their work with a laboratory model used by Dawson in which mouse brain cells were altered to spread small, thin fibers of alpha synuclein, a protein responsible for regulating mood and movement associated with the brain’s neurotransmitter dopamine.
When alpha synuclein proteins clump together, these clumps kill brain cells that produce dopaminewhich is a substance motion control key and the reduction of which causes the onset of Parkinson’s disease. As Dawson explains, the fibrous clusters of alpha-synuclein are very similar to those found in the brains of Parkinson’s patients.
The researchers found that irisin prevented the accumulation of alpha-synuclein clusters and associated brain cell death in mice. They then injected alpha-synuclein into the striatum, an area of the brain where dopamine-producing neurons extend, to generate an animal model of Parkinson’s disease, and after two weeks, injected them with a viral vector that increased irisin blood levels and what can cross the blood-brain barrier.
Mice with Parkinson’s disease show significant loss of dopamine-producing nerve cells, but treatment with irisin slows their loss. Specifically, mice given irisin showed a 25% loss of these cells compared to a 60% loss in mice given a placebo. Six months after treatment, the mice that received irisin had no muscle movement deficits, while those that received the placebo showed deficits in grip strength and in their ability to climb a pole.
The researchers also conducted studies of brain cells in mice given irisin that showed the exercise hormone also accelerated the transport and breakdown of alpha-synuclein through fluid-filled sacs called lysosomes in brain cells.
“If the utility of irisin is fulfilled, we can imagine it being developed into gene therapy or recombinant proteins,” says Dawson, referring to the field of drug development aimed at using cellular genetics to treat disease. “Because irisin is a naturally occurring peptide hormone and appears to have evolved to cross the blood-brain barrier, we believe it is worth further evaluating irisin as a potential therapy for Parkinson’s disease and other forms of neurodegeneration,” adds Spiegelman.
In fact, both scientists have applied for patents on the use of irisin in Parkinson’s disease, and Spiegelman founded the Boston-based biotech company Aevum Therapeutics Inc. to develop irisin to treat neurodegenerative diseases.