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Exercise hormone halts symptoms of Parkinson’s disease – Neuroscience News

Summary: Irisin, a hormone secreted into the blood during high endurance and aerobic exercise, reduces alpha-synuclein levels and restores movement in mouse models of Parkinson’s disease.

Source: Johns Hopkins Medicine

Researchers from Johns Hopkins Medicine and the Dana Farber Cancer Institute in Boston have shown that a hormone secreted into the blood during endurance, or aerobic exercise, reduces levels of a protein linked to Parkinson’s disease and stops movement problems in mice.

Parkinson’s disease, a neurological condition that causes loss of muscle and movement control, affects approximately 1 million people in the United States

If confirmed by further laboratory research and clinical trials, the researchers’ study of mice engineered to show symptoms of Parkinson’s disease could pave the way for a hormone-based therapy for Parkinson’s disease. irisin.

The researchers’ test results appeared on August 31 in Proceedings of the National Academy of Sciences.

Ted Dawson, MD, Ph.D., of Johns Hopkins Medicine, and Bruce Spiegelman, Ph.D., of Dana Farber, worked together to study the link between the exercise molecule irisin and Parkinson’s disease.

For unknown reasons, endurance exercise has long been shown to lessen the symptoms of Parkinson’s disease. Dawson, whose research focuses on neurodegenerative diseases including Parkinson’s disease, said one of the first clues to the link between exercise, Parkinson’s disease and irisin came from Spiegelman, whose first article on irisin was published in 2012 in Nature and subsequently in other scientific journals, showing that a protein called irisin peptide is released into the blood and increases with endurance exercise.

Over the past decade, other labs have found that exercise elevates irisin levels, and it’s interesting to examine the link between irisin and Alzheimer’s disease as well as Parkinson’s disease.

To test the effects of irisin on Parkinson’s disease, Dawson and Spiegelman’s teams started with a research model used by Dawson in which mouse brain cells are engineered to propagate small spindly fibers of alpha-synuclein. , a protein that regulates moods and brain-related movements. dopamine neurotransmitter.

When alpha-synuclein proteins clump together, these clusters kill brain cells that produce dopamine, a key trigger in Parkinson’s disease. The fibrous clumps of alpha-synuclein are very similar, Dawson says, to what’s found in the brains of people with Parkinson’s disease.

In the lab model, the researchers found that irisin prevented the buildup of alpha-synuclein clumps and associated brain cell death.

Next, the research teams tested the effects of irisin on mice engineered to show Parkinson-like symptoms. They injected alpha synuclein into an area of ​​the mouse’s brain, called the striatum, where dopamine-producing neurons extend.

Two weeks later, the researchers injected the mice with a viral vector that increased blood levels of irisin, which can cross the blood-brain barrier.

Six months later, the mice given irisin had no deficits in muscle movement, while those injected with a placebo showed deficits in grip strength and their ability to climb down a pole.

It shows a brain
In the lab model, the researchers found that irisin prevented the buildup of alpha-synuclein clumps and associated brain cell death. Image is in public domain

Additional brain cell studies in mice given irisin showed that the exercise hormone lowered levels of Parkinson’s disease-linked alpha-synuclein between 50% and 80%. The research team demonstrated that irisin also accelerates the transport and breakdown of alpha-synuclein via fluid-filled sacs called lysosomes in brain cells.

“If irisin proves useful, we might consider developing it into a recombinant gene or protein therapy,” says Dawson, referring to the broader field of drug development aimed at using cellular genetics to treat disease. Dawson is the Leonard and Madlyn Abramson Professor of Neurodegenerative Diseases, Professor of Neurology, and Director of the Johns Hopkins Institute for Cell Engineering.

“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,” adds Spiegelman.

Dawson and Spiegelman have filed patents on the use of irisin in Parkinson’s disease. Spiegelman created a biotechnology company, Aevum Therapeutics Inc., based in Boston, to develop irisin in treatments for neurodegenerative diseases.

Other scientists who contributed to the research include Tae-In Kam, Hyejin Park, Shih-Ching Chou, Yu Ree Choi, Devanik Biswas, Justin Wang, Yu Shin, Alexis Loder, Senthilkumar Karuppagounder and Valina Dawson at Johns Hopkins, and Jonathan Van Vranken. , Melanie Mittenbuhler, Hyeonwoo Kim, Mu A, and Christiane Wrann at Harvard Medical School.

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Funding: The research was funded by the JPB Foundation, Maryland Stem Cell Research Fund, Mark Foundation for Cancer Research, Damon Runyon Cancer Research Foundation and Deutsche Forschungsgemeinschaft.

About this Parkinson’s disease research news

Author: Vanessa Wasta
Source: Johns Hopkins Medicine
Contact: Vanessa Wasta – Johns Hopkins Medicine
Image: Image is in public domain

Original research: Free access.
“Improvement of α-synuclein-induced pathological Parkinson’s disease by irisin” by Ted Dawson et al. PNAS


Amelioration of α-synuclein-induced pathological Parkinson’s disease by irisin

Physical activity provides clinical benefit in Parkinson’s disease (PD). Irisin is an exercise-induced polypeptide secreted by skeletal muscle that crosses the blood-brain barrier and mediates some effects of exercise. Here, we show that irisin prevents α-synuclein (α-syn)-induced pathological neurodegeneration in the α-syn preformed fibril (PFF) mouse model of sporadic PD.

Intravenous administration of irisin via viral vectors following stereotaxic intrastriatal injection of α-syn PFF causes a reduction in pathological α-syn formation and prevents the loss of dopaminergic neurons and the decrease in striatal dopamine. Irisin also significantly reduced α-syn PFF-induced motor deficits as assessed behaviorally by the grip and grip strength test.

Sustained recombinant irisin treatment of primary cortical neurons attenuated α-syn PFF toxicity by reducing α-syn phosphorylated serine 129 formation and neuronal cell death. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathological α-syn by enhancing endolysosomal degradation of pathological α-syn.

Our results highlight the therapeutic modification potential of irisin in PD.

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