Overview: Irisin, a hormone secreted into the blood during high endurance and aerobic exercise, reduces α-synuclein levels and restores exercise in a mouse model of Parkinson’s disease.
sauce: johns hopkins medicine
Researchers at Johns Hopkins Medicine and the Dana-Farber Cancer Institute in Boston found that hormones secreted into the blood during endurance or aerobic exercise lowered the levels of a protein associated with Parkinson’s disease, and in mice. It has been shown to halt movement disorders.
Parkinson’s disease, a neurological disorder that causes loss of control over muscles and movements, affects approximately one million people in the United States.
If confirmed by additional laboratory studies and clinical trials, the researchers’ work in mice engineered to have Parkinson’s symptoms could pave the way for Parkinson’s disease treatments based on the hormone irisin. I have.
The results of the researchers’ tests were posted on August 31st. Proceedings of the National Academy of Sciences.
Ted Dawson, MD, Ph.D. of Johns Hopkins Medicine and Bruce Spiegelman, Ph.D. of Dana Farber collaborated to examine the link between the motor molecule irisin and Parkinson’s disease.
For unknown reasons, endurance exercise has long been found to alleviate symptoms of Parkinson’s disease.Dr. Dawson, whose research has focused on neurodegenerative diseases, including Parkinson’s disease, said one of his first clues to a link between exercise, Parkinson’s disease and irisin was the first paper on irisin published in 2012. of Nature Later, other scientific journals showed that proteins called irisin peptides were released into the blood and increased with endurance exercise.
Over the past decade, other research organizations have found that exercise increases irisin levels, and there is interest in examining the relationship between irisin and Alzheimer’s and Parkinson’s diseases.
To test the effects of irisin on Parkinson’s disease, Dawson and Spiegelman’s team started with the research model Dawson used. In this model, mouse brain cells are engineered to spread out small, thin fibers of alpha-his synuclein, a brain-associated protein that regulates mood and movement. neurotransmitter dopamine.
When alpha-synuclein proteins aggregate, these clusters kill brain cells that produce dopamine. This is the primary trigger for Parkinson’s disease. The fibrous masses of alpha-synuclein are very similar to those found in the brains of people with Parkinson’s disease, says Dawson.
In laboratory models, researchers found that irisin prevented the accumulation of alpha-synuclein clumps and associated brain cell death.
Next, the research team tested the effects of irisin on mice engineered to have Parkinson’s disease-like symptoms. was injected.
Two weeks later, the researchers injected mice with a viral vector that increased blood levels of irisin, which can cross the blood-brain barrier.
After 6 months, the irisin-treated mice had no muscle movement impairments, while the placebo-injected mice had impaired grip strength and ability to descend the pole.
Additional studies on brain cells in mice given irisin showed that exercise hormone reduced levels of alpha-synuclein, which is associated with Parkinson’s disease, by 50% to 80%. We have also demonstrated that it facilitates the transport and degradation of alpha-synuclein via a liquid-filled sac called
“If the utility of irisin is successful, you can imagine it being developed into a genetic or recombinant protein therapy,” Dawson said, referring to the development of drugs aimed at using cytogenetics to treat disease. It mentions that the field is expanding. 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 that appears to have evolved to cross the blood-brain barrier, we are interested in using irisin as a potential treatment for Parkinson’s disease and other forms of neurodegeneration. We think it’s worth continuing to evaluate,” adds Spiegelman.
Dawson and Spiegelman filed a patent for the use of irisin in Parkinson’s disease. Spiegelman founded the Boston-based biotechnology company Aevum Therapeutics Inc. to develop irisin as a therapeutic for neurodegenerative diseases.
Other scientists who contributed to this study include Tae-In Kam, Hyejin Park, Shih-Ching Chou, Yu Ree Choi, Devanik Biswas, Justin Wang, Yu Shin, Alexis Loder, Senthilkumar Karuppagounder, and Valina from Johns Hopkins University. Dawson, Jonathan Van Vranken included. Melanie Mittenbuhler, Hyeonwoo Kim, Mu A, and Christiane Wrann from Harvard Medical School.
See also
Funding: This study 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
sauce: johns hopkins medicine
contact: Vanessa Wasta – Johns Hopkins Medicine
image: image is public domain
Original research: open access.
“Amelioration of pathological alpha-synuclein-induced Parkinson’s disease by irisin” by Ted Dawson et al. PNAS
Overview
Improvement of pathological α-synuclein-induced Parkinson’s disease by irisin
Physical activity confers clinical benefits in Parkinson’s disease (PD). Iricin is an exercise-induced polypeptide secreted by skeletal muscle that crosses the blood-brain barrier and mediates certain effects of exercise. Here we show that irisin prevents pathological α-synuclein (α-syn)-induced neurodegeneration in an α-syn preformed fibril (PFF) mouse model of sporadic PD.
Viral vector-mediated intravenous delivery of irisin following stereotactic intrastriatal injection of α-syn PFF caused a decrease in the formation of pathologic α-syn, preventing loss of dopamine neurons and a drop in striatal dopamine . Irisin also significantly reduced α-syn PFF-induced motor deficits as behaviorally assessed by pole and grip strength tests.
Recombinant continuous 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 promoting its endolysosomal degradation.
Our findings highlight the therapeutic disease-modifying potential of irisin in PD.
