Exercise hormone may point toward potential cure

A person with a prosthetic leg wearing athletic clothing exercises outdoors in a parkShare on Pinterest
One study found that an exercise-induced hormone can reduce levels of a protein responsible for causing Parkinson’s symptoms. milanvirijevic/Getty Images
  • Parkinson’s disease is a progressive, neurodegenerative disease that affects more than 8.5 million people worldwide.
  • Symptoms such as tremors, muscle stiffness, slow movements, and cognitive impairment gradually worsen over time.
  • Some medications can relieve symptoms and improve quality of life, but there is currently no cure.
  • New research has found that a hormone produced during exercise reduces levels of the protein responsible for Parkinson’s symptoms.
  • The finding in mice could point to new treatments for the disease.

According to that World Health Organization (WHO), Parkinson’s disease (PD), a degenerative disease of the brain, is increasing faster than any other neurological disorder. Global prevalence has doubled in the last 25 years.

Symptoms of Parkinson’s develop slowly, worsen over time, and may include:

  • Tremble
  • Coordination and balance disorders
  • a loss of smell
  • gear changes
  • Changes in the nerves that control the muscles of the face
  • sleep disturbance
  • Mood swings, including depression
  • fatigue

There is currently no cure for the disease, although medication, occupational therapy, and speech therapy exercise can relieve symptoms.

Many of the symptoms become due to the accumulation of alpha synuclein Clumps that lead to the death of brain cells. A new study in mice, published in PNAS, has found that a hormone produced during aerobic exercise can prevent these lumps from forming.

“The results of this study are significant because while we know that physical activity and exercise are beneficial for people with Parkinson’s, it is currently unclear how this affects the cells and processes in the brain that contribute to the symptoms of the disease. This study sheds light on how a hormone produced during exercise may help protect vital brain cells from dying in Parkinson’s disease.”

– dr Katherine Fletcher, Research Communications Manager at Parkinson UK.

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Studies have shown that exercise can improve cognitive function and benefit those with Parkinson’s or Parkinson’s disease Alzheimer. Recent research identified irisin, a molecule released into the blood during endurance exercise, that may contribute to this benefit.

Because irisin is cleared in the same way in humans and mice, researchers at Johns Hopkins Medicine and the Dana-Farber Cancer Institute in Boston created a mouse model of Parkinson’s disease to study it further.

First, the researchers engineered mouse brain cells to produce alpha-synuclein fibers. When this protein forms clumps, like those found in the brains of people with Parkinson’s, the clumps kill dopamine production neurons.

The researchers administered irisin to these nerve cells in vitro and found that the alpha-synuclein fibers did not clump. The irisin also prevented brain cell death.

After the in vitro success, the researchers moved on to experiments on live mice, which were manipulated to exhibit 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 not injected with irisin showed muscle weakness. They had reduced grip strength and were less able to descend a pole.

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The mice that received the irisin had no deficits in muscle movement.

The researchers found that irisin given by injection had crossed the line blood-brain barrier and blocks the formation of alpha-synuclein clumps. Crucially, irisin had no effect on alpha-synuclein monomers, which were thought to be important transmission of nerve impulses.

When researchers analyzed brain tissue from mice, they found that clumps of alpha-synuclein were reduced by up to 80% in mice given irisin compared to those given placebo.

Further research showed that this effect was due to the lysosomal breakdown of clumps of alpha-synuclein, which the researchers believed was promoted by irisin.

They state: “Our demonstration that irisin reduces pathological α-syn is particularly relevant to the pathogenesis of PD and related α-synucleinopathies, since pathological α-syn appears to be the most important pathogenic factor of these disorders.”

“Given that irisin is a naturally produced peptide hormone and appears to have evolved to cross the blood-brain barrier, we think it is reasonable to continue evaluating irisin as a potential therapy for Parkinson’s and other forms of neurodegeneration.” said corresponding author Dr. Bruce Spiegelman, Ph.D. from the Dana Farber Cancer Institute.

Although this study was conducted in mice, irisin is also secreted from muscle and skeletal tissue in humans during exercise. However, exercise alone may not produce enough amounts to produce these effects, as Dr. Fletcher emphasized:

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“It is not clear from these results whether exercise alone would generate enough irisin to have a protective effect, or whether using other means of increasing 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 clots may therefore hold the key to its potential use as a treatment for Parkinson’s disease.

The researchers acknowledge that their findings are an early step in the search for an effective treatment for Parkinson’s disease, but are optimistic about its potential.

“It is very promising that it could be developed as a disease-modifying therapy to treat Parkinson’s disease. […] For any future human therapy it will be important to determine whether irisin can halt the progression of experimental Parkinson’s disease after neurological symptoms have begun and to determine the effects of irisin in other models of Parkinson’s.”

dr Fletcher welcomed the research but stressed the need for further studies: “The research has so far been conducted in a laboratory-based setting and needs to be further developed before paving the way for a future therapy that has the potential 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 gives hope as there are currently no treatments that can slow or stop the condition.”

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