A molecule induced by exercise can protect neurons directly
For generations, physicians have observed that movement heals in ways medicine alone cannot fully explain. Now, researchers at Mass General Brigham and the University Medical Center Hamburg-Eppendorf have traced one thread of that mystery to irisin, a hormone released by muscles during exercise, which appears to directly shield neurons from the degeneration at the heart of multiple sclerosis. Published in Nature Metabolism, the finding offers not only a biological explanation for exercise's benefits in MS patients, but a potential new therapeutic pathway for a disease whose current treatments address inflammation without halting the deeper loss of nerve tissue.
- Multiple sclerosis quietly destroys nerve fibers while existing treatments manage inflammation but leave neurodegeneration largely unchecked — a gap that has frustrated patients and researchers alike.
- The discovery that removing irisin from MS mouse models caused exercise's protective benefits to vanish entirely sharpened the urgency: this hormone is not incidental, it is the mechanism.
- Irisin reduced neuronal loss across the spinal cord, hippocampus, and retina, preserved synaptic connections, and reactivated a genetic program that defends neurons — a scope of protection that surprised even the research team.
- What distinguishes this finding is that irisin appears to act through direct neuroprotection rather than immune suppression, opening a pathway entirely separate from how current MS drugs work.
- The team now moves toward understanding irisin's molecular mechanics and testing whether it can be developed as a therapeutic, with particular hope for progressive MS forms where medicine has offered the least.
Scientists at Mass General Brigham and the University Medical Center Hamburg-Eppendorf have identified irisin — a hormone released by muscles during physical activity — as a key mechanism behind exercise's protective effects in multiple sclerosis. The research, published in Nature Metabolism, used mouse models to demonstrate that irisin reduced both clinical symptoms and neuronal loss across three regions of the central nervous system: the spinal cord, hippocampus, and retina. Crucially, when the hormone was removed, the benefits of exercise disappeared entirely; reintroducing it restored them, confirming irisin as the active agent.
Multiple sclerosis is a chronic autoimmune disease in which the immune system attacks myelin, the protective sheath around nerve fibers. While aerobic exercise has long been known to improve MS symptoms, the biological reason remained elusive. Current therapies reduce inflammation but have not proven effective at halting the underlying neurodegeneration — the gap this discovery begins to address.
Senior researcher Christiane D. Wrann, who leads the Neuroprotection in Exercise program at Mass General Brigham, noted that her team had previously linked irisin to cognitive protection in Alzheimer's models; this study extends that promise to MS. Lead author Sina C. Rosenkranz described the mechanism as fundamentally new — a direct neuroprotective action rather than peripheral immune suppression — a distinction that sets it apart from existing treatment strategies.
The researchers are candid that exercise's benefits in MS likely involve multiple biological pathways, and much about irisin's molecular workings remains to be understood. Their next steps focus on mapping that mechanism and exploring whether irisin can be developed as a therapeutic, especially for progressive MS forms where patients currently have the fewest options.
Scientists at Mass General Brigham and the University Medical Center Hamburg-Eppendorf have identified a molecular reason why exercise helps people with multiple sclerosis feel better. The answer lies in a hormone called irisin, released by muscles during physical activity, which appears to shield neurons from the damage that MS causes.
The research, published in Nature Metabolism, worked with mouse models of the disease. When irisin was present in the system, it reduced both the visible symptoms of MS and the loss of nerve cells. But when the researchers removed irisin entirely, the protective benefits of exercise vanished. Reintroducing the hormone restored those benefits, suggesting irisin itself was doing the protective work. The hormone reduced neuronal loss across three key regions of the central nervous system—the spinal cord, hippocampus, and retina—while also preserving synaptic connections and restoring a genetic program that shields neurons from harm.
Multiple sclerosis is a chronic autoimmune disease in which the body's own immune system attacks myelin, the insulating sheath around nerve fibers in the brain and spinal cord. Current treatments suppress inflammation but have not proven effective at stopping the underlying neurodegeneration. Aerobic exercise has been shown to improve symptoms in MS patients, yet until now, the exact biological mechanism remained unclear. This study offers a concrete answer: irisin.
Christiane D. Wrann, the senior researcher leading the Neuroprotection in Exercise program at Mass General Brigham, emphasized the significance of the finding. The team had previously shown that irisin improves cognitive function and reduces neuroinflammation in mouse models of Alzheimer's disease. This new work extends that promise to MS, a different neurodegenerative condition entirely. Wrann stated that the results reinforce the possibility that irisin could protect neurons across multiple types of degenerative brain diseases, not just MS.
What makes the finding particularly striking is that irisin appears to work through direct neuroprotection rather than by suppressing the peripheral immune system. Sina C. Rosenkranz, the study's lead author, called this mechanism fundamentally new—a direct way that exercise influences neurodegeneration in MS. His colleague Ruxandra F. Sîrbulescu, a neuroimmunologist, noted that the hormone's protective effects on neurons themselves were distinct from any immune-dampening action, suggesting a pathway independent of the inflammatory suppression that current MS drugs target.
The researchers acknowledge that much remains to be understood. The benefits of exercise in MS are complex and likely involve multiple biological pathways, not irisin alone. The team plans to continue investigating how irisin's protective mechanism works at the molecular level and to explore whether the hormone could be developed as a therapeutic agent, particularly for progressive forms of MS where current treatments have limited effectiveness. The work opens a door to a new class of potential treatments based on a molecule the body already produces naturally during physical activity.
Notable Quotes
A molecule induced by exercise can protect neurons directly in an MS model, revealing a fundamentally new mechanism by which exercise influences neurodegeneration— Sina C. Rosenkranz, lead author and head of behavioral interventions group at UKE
We are optimistic that our study will pave the way for developing irisin as a therapeutic, particularly for progressive multiple sclerosis— Christiane D. Wrann, senior researcher and leader of the Neuroprotection in Exercise program at Mass General Brigham
The Hearth Conversation Another angle on the story
Why does it matter that irisin works through direct neuroprotection rather than immune suppression?
Because current MS drugs work by quieting the immune system—they reduce the attack on myelin. But they don't stop the neurons from dying once the damage is done. Irisin seems to protect the neurons themselves, independent of immunity. That's a different target entirely.
So exercise was already helping people with MS, but nobody knew why?
Exactly. Doctors observed that aerobic exercise improved symptoms. But the mechanism was a black box. Now we have a candidate explanation: when you exercise, your muscles release irisin, and irisin shields neurons from degeneration.
If irisin is so protective, why doesn't the body just make more of it naturally in MS patients?
That's the question. The study doesn't answer it. It's possible that MS patients don't produce enough irisin, or that their neurons don't respond to it properly, or that the disease overwhelms the protection it offers. That's what future research will need to explore.
Could you just give someone irisin as a drug instead of making them exercise?
That's the hope. But irisin is a hormone, which means it's a protein. Proteins are fragile—they break down in the stomach, they don't cross the blood-brain barrier easily. Developing it as a therapeutic is a different challenge than discovering it works.
What about people with progressive MS, the kind that gets steadily worse?
That's where the researchers see the most promise. Current drugs don't slow progression well. If irisin can be turned into a therapy, it might offer a new option for patients who have run out of other treatments.
Does this mean people with MS should start exercising more?
The researchers are careful not to oversell it. Exercise helps, and now we know one reason why. But the benefits are complex—multiple factors at work. This study doesn't change the advice to exercise. It just explains part of why it works.