Summary: <\/strong>A neuroimmunology study uncovered the cellular mechanism decoding why exercise improves neurological symptoms in multiple sclerosis (MS). The research demonstrates that irisin, a hormone released by muscles during physical exertion, exerts a powerful, direct neuroprotective effect within the central nervous system.<\/p>\n By testing a mouse model of MS, investigators proved that irisin actively shields neurons from inflammation-driven neurodegeneration, decreases synaptic loss, and restores protective gene expression, providing a promising novel therapeutic bullseye for progressive forms of the disease.<\/p>\n Key Facts<\/strong><\/p>\n Source: <\/strong>Mass General<\/p>\n A new study offers clues as to why exercise can improve neurological symptoms in people with multiple sclerosis (MS). <\/strong><\/p>\n The study, led by investigators from\u00a0Mass General Brigham\u00a0and University Medical Center Hamburg-Eppendorf (UKE), examined levels of the exercise hormone irisin in a mouse model of multiple sclerosis.<\/p>\n Researchers found that irisin reduced both clinical symptoms and the loss of neurons in the experimental model. Additionally, when irisin was removed, the protective effects of exercise disappeared.<\/p>\n Taken together, the researchers\u2019 findings suggest that irisin can protect neurons from inflammation-driven neurodegeneration, offering a potential target for future MS therapies.<\/p>\n Results are published in\u00a0Nature Metabolism.<\/em><\/p>\n \u201cWe are optimistic that our study will open up further developments of irisin as a therapeutic for, in particular, progressive MS,\u201d said senior and corresponding author\u00a0Christiane D. Wrann, DVM, PhD, a neuroscientist and leader of the Program in Neuroprotection in Exercise at\u00a0Mass General Brigham Neuroscience Institute\u00a0and the\u00a0McCance Center for Brain Health\u00a0at Massachusetts General Hospital.<\/p>\n \u201cOur findings strengthen the argument that irisin can help protect neurons in the context of multiple types of neurodegenerative diseases.\u201d \u00a0<\/p>\n MS is a chronic, autoimmune-mediated neurodegenerative disease in which the immune system attacks the myelin sheaths that swath neurons in the brain and spinal cord. Current therapies for MS reduce inflammation but do not adequately prevent neurodegeneration. Research from other groups has shown that aerobic exercise can improve MS symptoms, but the exact mechanisms have been unknown.<\/p>\n Wrann and colleagues have previously shown that the hormone irisin, produced by muscles during exercise, can improve cognitive function and neuroinflammation in mouse models of\u00a0Alzheimer\u2019s disease. In their new federally funded study of MS, researchers also found evidence of neuroprotective effects.<\/p>\n In the MS model, deleting irisin canceled out the protective effects of exercise while adding irisin back rescued neurons and improved disease outcomes. Irisin reduced neuronal loss in three central nervous system compartments: spinal cord, hippocampus, and retina, reduced loss of synapses and restored a neuroprotective gene program.<\/p>\n \u201cWhat we find particularly exciting is that an exercise-induced molecule can directly protect neurons in a mouse model of multiple sclerosis, revealing a fundamentally new mechanism by which exercise can influence neurodegeneration in MS,\u201d said Sina C. Rosenkranz, MD, first author and head of the Behavioral Interventions group at the Institute for Neuroimmunology and Multiple Sclerosis (INIMS) at UKE. Rosenkranz is a former postdoctoral fellow in the Wrann lab.<\/p>\n \u201cInterestingly, in the current study we did not find a direct suppressive effect of irisin on peripheral immunity, but rather direct neuroprotective effects,\u201d said\u00a0Ruxandra F. S\u00eerbulescu, PhD,\u00a0co-senior author on the study, a neuroimmunologist at Mass General Brigham Neuroscience Institute and leader of the Regenerative Medicine program at the\u00a0Vaccine and Immunotherapy Center.<\/p>\n The authors note that more research is needed to understand how irisin\u2019s protective mechanism works. They also note that it\u2019s important to remember that the benefits of exercise in multiple sclerosis are complex and likely involve multiple factors, not just irisin alone. The team plans to continue investigating the hormone\u2019s effects and mechanisms in future studies.<\/p>\n Authorship:\u00a0<\/strong>In addition to Wrann, Rosenkranz, and S\u00eerbulescu, co-authors include Joana F. da Rocha, Luis Moreira, Pius Schlachter, Jasmina Bier, Kaela Healy, Daniela Neves Silva, Mohamed Ariff Iqbal, Marjan Gharagozloo, Yueyue Xiong, Matthew A. Murphy, Helena C. Lichtenfeld, Lukas Raich, Michaela Schweizer, Asude Erta\u015f, Marcel S. Woo, Vanessa Vieira, Samuel E. Honeycutt, James P. White, Gregory A. Wyant, Manuel A. Friese, and Peter A. Calabresi.<\/p>\n Disclosures:\u00a0<\/strong>Wrann holds a patent related to irisin (WO2015051007A1). Wrann is an academic co-founder and consultant for Aevum Therapeutics. Wrann has a financial interest in Aevum Therapeutics, a company developing drugs which harness the protective molecular mechanisms of exercise to treat neurodegenerative and neuromuscular disorders. Wrann received honoraria from Novartis outside the scope of this work. Wrann\u2019s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. Rosenkranz has received speaker honoraria from Merck, Roche and Sanofi, all outside of this work. Calabresi has received consulting fees from Lilly and Novartis and is PI on a grant to JHU from Genentech. Woo received honoraria from Lilly and Eisai outside the scope of this work. Funding:\u00a0<\/strong>This work was supported in part by the National Institutes of Health (NS117694, AG062904, AG064580, AG072054, NS117598, NS041435, R56AG056664, T32AG07057); the Cure Alzheimer\u2019s Fund; a SPARC Award from the McCance Center for Brain Health; the Hassenfeld Clinical Scholar Award; the Claflin Distinguished Scholar Award; the Boehringer Ingelheim Fonds travel grant; the Advanced Clinician\u2013Scientist Fellowship from the Federal Ministry of Education and Research, Germany (iSTAR 01EO2106); the Gemeinn\u00fctzige Hertie\u2011Stiftung (P1200012, P1250014); the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation\u2014project 523862973); a National MS Society Career Transition Grant (TA\u20112104\u201137423); and the Else\u2011Kr\u00f6ner\u2011Fresenius\u2011Foundation.<\/p>\n A<\/strong>: It is a stunning display of cross-system biology. When you exercise, your working muscles act like an endocrine organ, secreting a specialized hormone called irisin straight into your bloodstream. Mass General Brigham and UKE discovered that irisin travels straight to the central nervous system. Instead of trying to fix your immune system, irisin goes directly to work on your nerve cells, acting like a structural shield that keeps neurons in your spinal cord, hippocampus, and retina from breaking down under an autoimmune attack.<\/p>\n<\/div>\n A<\/strong>: Current MS therapies do a fantastic job of suppressing the immune system to quiet down localized inflammation, but they are notoriously poor at stopping the actual physical degeneration and death of neurons over time. That is why progressive MS remains so incredibly difficult to treat. Irisin represents a fundamentally new mechanism because it doesn\u2019t suppress your peripheral immunity; instead, it acts as a direct neuroprotectant, offering a brand-new way to keep neurons alive and synapses intact when inflammation hits.<\/p>\n<\/div>\n A<\/strong>: No, and it is vital to look at the full picture. While this mouse model study explicitly proves that irisin directly rescues neurons and is required to lock in the brain-boosting benefits of exercise, multiple sclerosis is an intricate, multifactorial disease. Working out triggers a highly complex symphony of biological changes throughout your body, meaning irisin isn\u2019t acting entirely alone. The team is moving forward with deeper studies to translate these molecular discoveries into targeted therapies, specifically for progressive MS.<\/p>\n<\/div>\n<\/div>\n Author:\u00a0<\/strong>Brandon Chase<\/a>\n
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<\/picture>Key Questions Answered:<\/h3>\n
Editorial Notes:<\/h3>\n
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About this multiple sclerosis research news<\/h2>\n
Source:\u00a0<\/strong>Mass General<\/a>
Contact:\u00a0<\/strong>Brandon Chase \u2013 Mass General
Image:\u00a0<\/strong>The image is credited to Neuroscience News<\/p>\n