Newswise – 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 lowers levels of a protein linked to Parkinson’s disease and stops movement problems in mice.
Parkinson’s disease, a neurological disease 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.
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 given a placebo showed deficits in grip strength and their ability to step off a pole.
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 Johns Hopkins Cell Engineering Institute.
“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.
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.