Parkinson's: Exercise hormone may point toward potential cure2022-10-14
- Parkinson’s disease is a progressive, neurodegenerative condition that affects more than 8.5 million people worldwide.
- Symptoms, such as tremors, muscle rigidity, slow movement, and cognitive impairment, gradually worsen over time.
- Some medications can alleviate symptoms and improve quality of life, but there is currently no cure.
- New research has found that a hormone produced during exercise reduces protein levels responsible for Parkinson’s symptoms.
- The finding in mice may point toward new treatments for the disease.
According to the World Health Organization (WHO), Parkinson’s disease (PD), a degenerative condition of the brain, is increasing faster than any other neurological disorder. Worldwide, the prevalence has doubled in the past 25 years.
Symptoms of Parkinson’s develop slowly, worsening over time, and may include the following:
- Impaired coordination and balance
- a loss of sense of smell
- gait changes
- changes in the nerves that control face muscles
- sleep problems
- mood changes, including depression
There is currently no cure for the disease, although medications, occupational therapy, speech therapy, and exercise can alleviate the symptoms.
Many of the symptoms may be due to the accumulation of alpha-synuclein clumps, which lead to brain cell death. A new study in mice, published in PNAS, has found that a hormone produced during aerobic exercise can prevent the formation of these clumps.
“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.”
– Dr. Katherine Fletcher, Research Communications Manager at Parkinson’s UK.
Studies have shown that exercise may improve cognitive function and benefit those with Parkinson’s or Alzheimer’s. Recent research identified irisin, a molecule secreted into the blood during endurance exercise, which may contribute to this benefit.
As irisin is secreted in the same way in humans and mice, researchers from Johns Hopkins Medicine and the Dana-Farber Cancer Institute in Boston created a mouse model of Parkinson’s to investigate it further.
First, the researchers engineered mouse brain cells to produce fibers of alpha-synuclein. When this protein forms clumps, as found in the brains of people with PD, the clumps kill dopamine-producing neurons.
The researchers administered irisin to these nerve cells in vitro and found that the alpha-synuclein fibers did not form clumps. The irisin also prevented the brain cells from dying.
Muscle movement effects
After the in vitro success, the researchers moved to experiments in live mice engineered to have Parkinson’s-like symptoms.
First, they injected alpha-synuclein into an area of the mouse brain called the striatum, which has many dopamine-producing neurons. Two weeks later, they injected irisin into the tail vein of the mice.
After 6 months, mice that were not injected with irisin showed muscle impairment. They had reduced grip strength and were less able to descend a pole.
The mice that had received the irisin had no muscle movement deficits.
The researchers found that irisin administered by injection had crossed the blood-brain barrier and blocked the formation of alpha-synuclein clumps. Crucially, irisin had no effect on alpha-synuclein monomers thought to be important in transmitting nerve impulses.
Changes in the brain
When researchers analyzed brain tissue from the mice, they found that alpha-synuclein clumps were reduced by up to 80% in mice given irisin, compared with those given placeboes.
Further investigations showed that this effect was due to lysosomal degradation of the alpha-synuclein clumps, which the researchers suggest was promoted by irisin.
They state: “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.”
Parkinson’s treatment potential
“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,” said corresponding author Dr. Bruce Spiegelman, Ph.D. of Dana-Farber Cancer Institute.
Although this study was carried out in mice, irisin is also secreted by muscle and skeletal tissues in people during exercise. However, exercise alone may not produce sufficient quantities to have these effects, as Dr. Fletcher pointed out:
“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 finding that injected irisin can cross the blood-brain barrier to reach the alpha-synuclein clumps may, therefore, be key to its potential use as a treatment for Parkinson’s disease.
Early step in the search for PD treatment
The researchers acknowledge that their findings are an early step in the hunt for an effective treatment for Parkinson’s disease but are optimistic about its potential.
“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.”
While welcoming the research, Dr. Fletcher stressed the need for further studies: “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.”
However, she added: “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.”
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