Parkinson's: exercise hormone could point to potential cure

Parkinson’s: exercise hormone could point to potential cure

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A study has found that a hormone induced by exercise can reduce levels of a protein responsible for symptoms of Parkinson’s disease. 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 rigidity, slow movements and cognitive impairment, gradually worsen over time.
  • Certain medications can relieve symptoms and improve quality of life, but there is currently no cure.
  • New research has revealed that a hormone produced during exercise reduces levels of proteins responsible for the symptoms of Parkinson’s disease.
  • The finding in mice may point to new treatments for the disease.

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

Symptoms of Parkinson’s disease develop slowly, get worse over time, and can include the following:

  • tremors
  • Coordination and balance disorders
  • a loss of smell
  • gait changes
  • changes in the nerves that control the muscles of the face
  • sleep problems
  • mood changes, including depression
  • fatigue

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

Many symptoms must be due to the accumulation of alpha-synuclein clusters, which 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 clumps from forming.

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

– Dr Katherine Fletcher, Head of Research Communications at Parkinson’s UK.

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

Because 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 disease to study it further.

First, the researchers engineered mouse brain cells to produce alpha-synuclein fibers. When this protein forms clumps, as found in the brains of people with PD, 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 form clumps. Irisin also prevented brain cells from dying.

After the in vitro success, the researchers moved on to experiments in live mice designed to show Parkinson-like symptoms.

First, they injected alpha-synuclein into an area of ​​the mouse brain called the striatum, which contains many dopamine-producing neurons. Two weeks later, they injected irisin into the mice’s tail veins.

After 6 months, the mice that had not received an irisin injection showed muscle damage. They had reduced grip strength and were less able to descend a pole.

The mice that had received irisin had no deficit in muscle movement.

The researchers found that the irisin given by injection crossed the blood-brain barrier and blocked the formation of alpha-synuclein clusters. Basically, irisin had no effect on alpha-synuclein monomers considered important in transmit nerve impulses.

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

Further research showed that this effect was due to lysosomal breakdown of alpha-synuclein clusters, which the researchers believe 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 primary pathogenic driver of these disorders.”

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

Although this study was conducted in mice, irisin is also secreted by muscle and skeletal tissues in people during exercise. However, exercise alone may not produce sufficient amounts to have these effects, as Dr. Fletcher pointed out:

“Based on these results, it is unclear whether exercise alone would generate enough irisin to have protective effects or whether using other means to stimulate this hormone might be a more realistic treatment option in the future. ‘coming.”

The discovery that injected irisin can cross the blood-brain barrier to reach alpha-synuclein clusters may therefore hold the key to its potential use as a treatment for Parkinson’s disease.

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

“There is great promise that it could be developed as a disease-modifying therapy for the treatment of PD. […] It will be important for any future human therapy to determine if irisin can arrest the progression of experimental PD after the onset of neurological symptoms and to determine the effects of irisin in other models of PD.

While welcoming the research, Dr Fletcher stressed the need for further studies: “Research has so far been carried out in a laboratory environment and will need to be developed further before it paves the way for future therapy. which may be able to slow or stop the condition of people with Parkinson’s disease.

However, she added: “Anything that shows promise for protecting brain cells in Parkinson’s disease offers hope, as there is currently no treatment that can slow or stop the disease.”

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