Physical 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 numerous diseases. New research has now shown that irisin, a hormone released into the blood by skeletal muscles and other tissues during aerobic or resistance exercise, decreases levels of a protein associated with Parkinson’s disease – alpha-synuclein. toxic – and slows the symptoms of Parkinson’s in mice.
If this finding is corroborated in new studies and clinical trials, it could serve as a basis for using irisin as a therapeutic molecule against Parkinson’s and other neurodegenerative diseases. The research has been carried out by scientists from Johns Hopkins Medicine and the Dana Farber Cancer Institute in Boston (USA) in mice that had been modified to have symptoms similar to those caused by Parkinson’s and their results have been published in Proceedings of the National Academy of Sciences (PNAS).
Using irisin to treat neurodegenerative diseases
Endurance exercise has long been known to relieve Parkinson’s symptoms, and in 2012 Dr. Bruce Spiegelman of Dana Farber published an article on irisin in Nature and other scientific journals noting that a protein called irisin peptide Irisin is released into the blood and increases with resistance exercise. In the last 10 years, several laboratories have discovered that exercising increases irisin levels in the blood, which has sparked interest in studying the relationship between this hormone and neurodegenerative pathologies such as Alzheimer’s or Parkinson’s.
Mice given irisin had no muscle movement deficits, but those given a placebo showed deficits in grip strength and in their ability to descend from a pole
Spiegelman and Dr. Ted Dawson, professor of neurology and director of the Johns Hopkins Institute for Cell Engineering, decided to investigate the link between this exercise hormone and Parkinson’s disease and began their work with a laboratory model used by Dawson in which brain cells of mice are altered to propagate small, thin fibers of alpha synuclein, a protein that is responsible for regulating moods and movements related to the brain neurotransmitter dopamine.
When alpha synuclein proteins clump together, those clumps eliminate brain cells that produce dopamine, which is a key substance for movement control and whose depletion leads to Parkinson’s disease. As explained by Dawson, the fibrous groups 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, and after two weeks they injected a viral vector, which increased irisin levels in the blood and can cross the blood-brain barrier.
The Parkinson’s mice showed significant loss of dopamine-producing nerve cells, but treatment with irisin slowed their loss. Specifically, mice given irisin showed a 25% loss of these cells compared to a 60% loss in mice given placebo. Six months after treatment, the mice that received irisin had no muscle movement deficits, while those that received a placebo showed deficits in grip strength and in their ability to descend a pole.
The researchers also conducted brain cell studies in the mice given irisin that showed that the exercise hormone also speeds up the transport and breakdown of alpha-synuclein through fluid-filled sacs called lysosomes in brain cells.
“If the utility of irisin is fulfilled, we could imagine it being developed into gene therapy or recombinant proteins,” says Dawson, referring to the field of drug development aimed at the use of cell genetics for the treatment of diseases. “Since irisin is a naturally occurring peptide hormone and appears to have evolved to cross the blood-brain barrier, we believe irisin is worth further evaluation as a potential therapy for Parkinson’s 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 has created the Boston-based biotech company Aevum Therapeutics Inc. to develop irisin into treatments for neurodegenerative diseases.
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