Exercise hormone stops symptoms of Parkinson’s disease

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

source: Johns Hopkins Medicine

Researchers from Johns Hopkins Medicine and the Dana-Farber Cancer Institute in Boston showed that a hormone released into the blood during aerobic exercise reduces levels of a protein linked to Parkinson’s disease and halts movement problems in mice.

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

If confirmed in additional lab research and clinical trials, the researchers’ study in mice engineered to develop symptomatic Parkinson’s disease could pave the way for an irisin-based treatment for Parkinson’s disease.

The results of the researchers’ tests came out on August 31 Proceedings of the National Academy of Sciences.

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

For unknown reasons, endurance exercises have long been found to relieve 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 and Parkinson’s disease and iris came from Spiegelmann, whose first paper on irisin was published in 2012 in temper nature And then in other scientific journals, it was shown that a protein called irisin peptide is released into the blood and increases with endurance exercise.

In the past decade, other laboratories have found that exercise raises irisin levels, and there is interest in looking at the relationship between Alzheimer’s disease and Alzheimer’s disease in addition to Parkinson’s disease.

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

When alpha-synuclein proteins clump, those clumps kill dopamine-producing brain cells, a major cause of Parkinson’s disease. The fibroblasts of alpha-synuclein are very similar to what’s found in the brains of people with Parkinson’s disease, Dawson says.

In the in vitro model, the researchers found that aricin prevents the buildup of alpha-synuclein clumps and the associated death of brain cells.

Next, the research teams tested the effects of irisin in mice engineered to display symptoms similar to Parkinson’s disease. They injected alpha-synuclein into an area of ​​the mouse’s brain, called the striatum, where dopamine-producing neurons expand.

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

After six months, the mice receiving irisin had no deficits in muscle movement, while the placebo-injected mice showed deficits in grip strength and ability to get off one of the electrodes.

This indicates a brain
In the in vitro model, the researchers found that aricin prevents the buildup of alpha-synuclein clumps and the associated death of brain cells. The image is in the public domain

Additional studies of brain cells in mice given irisin showed that the exercise hormone reduced levels of alpha-synuclein associated with Parkinson’s disease between 50% and 80%. The research team showed that irisin also speeds up the transport and degradation of alpha-synuclein via fluid-filled sacs called lysosomes in brain cells.

“If the benefit of irisin stops working, we can imagine developing it into a gene or recombinant protein therapy,” Dawson says, referring to the broad field of drug development aimed at using cytogenetics to treat disease. Dawson is the Leonard and Madeleine Abramson Professor of Neurodegenerative Diseases, and Professor of Neuroscience and Director of the Johns Hopkins Institute for Cell Engineering.

“Because irisin is a naturally produced peptide hormone that appears to have evolved to cross the blood-brain barrier, we believe it is useful to continue to evaluate irisin as a potential treatment for Parkinson’s disease and other forms of neurodegeneration,” Spiegelman adds.

Dawson and Spiegelman filed patents regarding the use of irisin in Parkinson’s disease. Spiegelman created the biotechnology company, Aevum Therapeutics Inc. Headquartered in Boston, to develop irisin into treatments for neurodegenerative disease.

Other scientists who contributed to the research included Tae-in-Kam, Heejin Park, Shih-Cheng Chu, Yoo Ri Choi, Devanik Biswas, Justin Wang, Yue Shen, Alexis Lauder, Sentelkumar Karupajion, Valina Dawson of Johns Hopkins University, and Jonathan Van Franken. . , Melanie Mittenbühler, Hyunwoo Kim, Mo A and Christian Ran at Harvard Medical School.

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

About Parkinson’s Disease Research News

author: Vanessa Wasta
source: Johns Hopkins Medicine
Contact: Vanessa Wasta – Johns Hopkins Medicine
picture: The image is in the public domain

original search: open access.
Improvement of Parkinson’s disease induced by alpha-synuclein by irisinWritten by Ted Dawson et al. PNAS


Improvement of Parkinson’s disease induced by alpha-synuclein 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 specific effects of exercise. Here, we demonstrate that irisin prevents pathological α-synuclein-induced neurodegeneration in a preformed fibroblast (PFF) mouse model of sporadic PD.

Intravenous iris delivery via viral vectors after intrapartum stereotaxic injection of α-syn PFF leads to a decrease in pathological α-syn formation, preventing loss of dopaminergic neurons and lowering of striatal dopamine. Irisin also significantly reduced α-syn PFF-induced motor deficits as assessed behaviorally by electrode and grip strength test.

Continuous recombinant iris treatment of primary cortical neurons attenuated the toxicity of α-syn PFF by reducing the formation of phosphorylated serine 129 for α-syn neuron and neuronal apoptosis. Tandem mass spectrometry and biochemical analysis revealed that irisin reduces pathological α-syn by enhancing intrinsic particle degradation of pathological α-syn.

Our findings highlight the potential for therapeutic irisin modulation in Parkinson’s disease.

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