Based on previous work demonstrating the positive effects of exercise on symptoms of Parkinson’s disease, researchers looked at how irisin, a hormone released during exercise, affected the accumulation of misfolded alpha-synuclein in a mouse model of Parkinson’s.
In the in vitro portion of the study, cells from mice were treated with preformed fibrils of alpha-synuclein, which prompt naturally occurring alpha-synuclein to misfold and aggregate. When irisin was administered in these cells, it prevented alpha-synuclein from forming into toxic clumps and protected nerve cells from dying.
In the in vivo portion of the study, preformed fibrils of alpha-synuclein were injected directly into the brains of mice to create a model of Parkinson’s disease. Mice later treated with irisin showed a 25% loss in dopamine-producing cells, compared to a 60% loss in untreated mice. Further, irisin prevented the turnover of dopamine and reduced motor deficits as measured by the pole and grip strength test. Researchers also demonstrated that one of the mechanisms by which irisin reduces the levels of toxic alpha-synuclein is through increased lysosomal uptake.
The study authors conclude that “…since irisin treatment was begun well after the pathogenic cascade was initiated by the α-syn injection, there is considerable promise that it might be developed as a disease-modifying therapy for the treatment of PD. Therefore, optimization of irisin delivery as a biologic therapy holds promise for the treatment of PD and other neurodegenerative disorders.”