Summary: Irisin, secreted into the bloodstream during high-intensity, aerobic exercise, reduces alpha-synuclein levels and restores Parkinson’s disease in mouse models.

Source: Johns Hopkins Medicine

Researchers at Johns Hopkins Medicine and the Dana Farber Cancer Institute in Boston found that the hormone injected during endurance or aerobic exercise reduced levels of a protein associated with Parkinson’s disease and stopped movement disorders in mice.

Parkinson’s disease, a neurological disease that causes people to lose control of their muscles and movements, affects about 1 million people in the US.

If confirmed in further laboratory research and clinical trials, the researchers’ study of the symptoms of Parkinson’s disease in mice could pave the way for a treatment for Parkinson’s disease based on the hormone IS.

The researchers’ tests They appeared on August 31 Proceedings of the National Academy of Sciences.

Johns Hopkins Medicine’s Ted Dawson, MD, PhD, and Dana Farber’s Bruce Spiegelman, PhD, worked together to look at the link between the exercise molecule iris and Parkinson’s disease.

For unknown reasons, endurance exercise has long been found to relieve the symptoms of Parkinson’s disease. Dawson, who specializes in neurodegenerative diseases including Parkinson’s disease, said one of the first clues to the link between exercise and Parkinson’s disease came from Spiegelman, whose first paper on Irene was published in 2012. Nature And then in other scientific journals, it is shown that a protein called irisin peptide is released into the blood and increases with endurance exercise.

Over the past decade, other laboratories have found that exercise increases irisin levels, and there is interest in investigating the relationship between irisin and Alzheimer’s disease as well as Parkinson’s disease.

To test Irene’s effects on Parkinson’s disease, Dawson and Spiegelman’s team started with the same study model Dawson used, in which rat brain cells spread small, spiny fibers of alpha-synuclein, a protein that regulates mood and brain-related activity. The neurotransmitter dopamine.

When alpha-synuclein proteins accumulate, these clumps kill brain cells that produce dopamine, which is key to Parkinson’s disease. It’s very similar to the fibrous clumps of alpha-synuclein found in the brains of people with Parkinson’s disease, Dawson says.

In a laboratory model, the researchers found that irisin prevents the accumulation of alpha-synuclein clumps and the death of brain cells associated with it.

Next, the research teams tested Irene’s effects on mice engineered to have Parkinson’s-like symptoms. Alpha-synuclein entered the striatum, an area of ​​the mouse brain where dopamine-producing neurons grow.

Two weeks later, the researchers injected Irene with a viral vector that could cross the blood-brain barrier and increase blood volume.

After six months, mice that received Irene had no muscle movement deficits, while those injected with placebo showed deficits in grip strength and pole climbing ability.

This shows the brain
In a laboratory model, the researchers found that irisin prevents the accumulation of alpha-synuclein clumps and the death of brain cells associated with it. The image is in the public domain.

Further studies of brain cells in mice given irisin showed that the exercise hormone reduced levels of alpha-synuclein, which is associated with Parkinson’s disease, by 50 percent to 80 percent. The research team showed that irisin speeds up the transport and degradation of alpha-synuclein in fluid-filled sacs called lysosomes in brain cells.

“If Irene’s utility comes out, we can imagine that it will turn into gene or recombinant protein therapy,” Dawson said, referring to the field of drug development aimed at using cellular genetics to treat disease. Dawson is the Leonard and Madeline Abramson Professor of Neurodegenerative Diseases, professor of neurology, and director of cell engineering at the Johns Hopkins Institute.

Spiegelman added, “If IS is a naturally occurring peptide hormone that appears to have evolved to protect the blood brain, we think it’s worth continuing to evaluate IS as a potential treatment for Parkinson’s and other types of neurodegenerative diseases.”

Dawson and Spiegelman have filed for a patent on the use of irisin in Parkinson’s disease. Spiegelman hired Boston-based Aevum Therapeutics Inc. to treat Irene for the neurodegenerative disease. He founded a biotechnology company called

Other scientists who contributed to the research included Tae-In Kam, Hyejin Park, Shih-Ching Chu, Yu Ri Choi, Devanik Biswas, Justin Wang, Yu Shin, Alexis Loder, Sentlikmar Karupagonder, and Valina Dawson at Johns Hopkins and Jonathan Van Vranken. , Melanie Mittenbuhler, Hyeonwoo Kim, Moo A, and Christine Wann at Harvard Medical School.

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This shows the psychedelic brain

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

So Parkinson’s disease research news

Author: Vanessa Wasta
Source: Johns Hopkins Medicine
Contact: Vanessa Wasta – Johns Hopkins Medicine
Image: The image is in the public domain.

Preliminary study: Open Access.
Pathological α-synuclein-induced Parkinson’s disease by ircin” by Ted Dawson et al PNAS


Pathological α-synuclein-induced Parkinson’s disease by ircin

Exercise 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 modulates certain types of exercise. Here, we show that irisin prevents pathological α-synuclein (α-syn)-induced neurodegeneration in the α-syn preformed fibril (PFF) mouse model of sporadic PD.

Intravenous delivery of irisin via a viral vector reduced pathologic α-syn formation following stereotaxic intrastriatal injection of α-syn PFF and prevented loss of dopamine neurons and reduced striatal dopamine. Furthermore, irisin inhibited α-syn PFF-induced motor deficits as assessed behaviorally by pole and grip strength tests.

Repeated continuous irene treatment of primary cortical neurons reduced α-syn PFF toxicity by reducing phosphorylated serine 129 of α-syn and neuronal cell death. Tandem mass spectrometry and biochemical analysis confirmed that irisin reduces pathological α-syn by enhancing endolysosomal degradation of pathological α-syn.

Our findings highlight the disease-modifying potential of irisin in PD.

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