Irisin Mediates the Effects of Physical Exercise on Parkinson's Disease Progression

Exercise is known to slow the progression of Parkinson's disease, or at least attenuate the symptoms. What is the underlying mechanism? Researchers here suggest that the myokine signal protein irisin accounts for much of this, by promoting greater removal of problematic α-synuclein aggregates. Parkinson's disease is associated with α-synuclein misfolding and consequent aggregation, these toxic versions of a normally helpful protein spreading through the central nervous system over time to cause cell death and dysfunction in vulnerable populations of neurons. Clearing misfolded α-synuclein seems a viable strategy, given the right approach, something much more potent than the effects of exercise.

Physical exercise is thought to have beneficial effects on the symptoms of Parkinson's disease (PD). Irisin is an exercise-induced myokine released into the circulation. We therefore tested whether irisin itself could have a beneficial effect on pathologic α-synuclein (α-syn) accumulation and concomitant neurodegeneration in PD.

Here, we show that irisin prevents pathologic α-synuclein (α-syn)-induced neurodegeneration in the α-syn preformed fibril (PFF) mouse model of sporadic PD. Intravenous delivery of irisin via viral vectors following the injection of α-syn PFF cause a reduction in the formation of pathologic α-syn and prevented the loss of dopamine neurons and lowering of striatal dopamine. Irisin also substantially reduced the α-syn PFF-induced motor deficits as assessed behaviorally by the pole and grip strength test.

In vitro, recombinant sustained irisin treatment of primary cortical neurons attenuated α-syn PFF toxicity by reducing the formation of phosphorylated serine 129 of α-syn and neuronal cell death. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathologic α-syn by enhancing endolysosomal degradation of pathologic α-syn. Our findings highlight the potential for therapeutic disease modification of irisin in PD.



Ah... 'Contributed by Bruce M. Spiegelman'.

'...irisin was patented by Boström and Spiegelman, then licenced to a pharma company and scheduled to go from 2014 on for clinical treatment of obesity and type 2 diabetes. If you have not heard of this miracle cure yet, it is because very soon doubts arose about what these two scientists claimed to have discovered.'

I'm sure this time it will be different. Parkinson's none the less. ;p

Posted by: Jones at September 21st, 2022 4:55 AM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.