Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Prim. 3, 17013 (2017).
Stocchi, F. et al. Parkinson disease therapy: current strategies and future research priorities. Nat. Rev. Neurol. 20, 695–707 (2024).
Steib, S. et al. A single bout of aerobic exercise improves motor skill consolidation in Parkinson’s disease. Front. Aging Neurosci. 10, 328 (2018).
Fang, X. et al. Association of levels of physical activity with risk of Parkinson disease: a systematic review and meta-analysis. JAMA Netw. Open 1, e182421 (2018).
Langeskov-Christensen, M. et al. Exercise as medicine in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 95, 1077–1088 (2024).
Walzik, D. et al. Molecular insights of exercise therapy in disease prevention and treatment. Signal Transduct. Target. Ther. 9, 138 (2024).
Petzinger, G. M. et al. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease. Lancet Neurol. 12, 716–726 (2013).
Yao, H. et al. Exercise training upregulates CD55 to suppress complement-mediated synaptic phagocytosis in Parkinson’s disease. J. Neuroinflammation 21, 246 (2024).
Li, Z. et al. Exercise attenuates mitochondrial autophagy and neuronal degeneration in MPTP induced Parkinson’s disease by regulating inflammatory pathway. Folia Neuropathol. 61, 426–432 (2023).
Safdar, A., Saleem, A. & Tarnopolsky, M. A. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat. Rev. Endocrinol. 12, 504–517 (2016).
Ruiz-González, D. et al. Effects of physical exercise on plasma brain-derived neurotrophic factor in neurodegenerative disorders: a systematic review and meta-analysis of randomized controlled trials. Neurosci. Biobehav. Rev. 128, 394–405 (2021).
Soke, F. et al. Effects of task-oriented training combined with aerobic training on serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1β levels in people with Parkinson’s disease: a randomized controlled study. Exp. Gerontol. 150, 111384 (2021).
Speck, A. E. et al. Treadmill exercise attenuates L-DOPA-induced dyskinesia and increases striatal levels of glial cell-derived neurotrophic factor (GDNF) in hemiparkinsonian mice. Mol. Neurobiol. 56, 2944–2951 (2019).
Pérez-Domínguez, M., Tovar-Y-Romo, L. B. & Zepeda, A. Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior. Rev. Neurosci 29, 1–20 (2018).
Chuang, C.-S. et al. Modulation of mitochondrial dynamics by treadmill training to improve gait and mitochondrial deficiency in a rat model of Parkinson’s disease. Life Sci. 191, 236–244 (2017).
Ebanks, B. et al. The dysregulated Pink1- Drosophila mitochondrial proteome is partially corrected with exercise. Aging 13, 14709–14728 (2021).
Cadet, P. et al. Cyclic exercise induces anti-inflammatory signal molecule increases in the plasma of Parkinson’s patients. Int. J. Mol. Med. 12, 485–492 (2003).
Mak, M. K. Y. & Wong-Yu, I. S. K. Six-month community-based brisk walking and balance exercise alleviates motor symptoms and promotes functions in people with Parkinson’s disease: a randomized controlled trial. J. Parkinsons Dis. 11, 1431–1441 (2021).
van der Kolk, N. M. et al. Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson’s disease: a double-blind, randomised controlled trial. Lancet Neurol. 18, 998–1008 (2019).
Schenkman, M. et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 75, 219–226 (2018).
Chen, Y.-H. et al. Exercise ameliorates motor deficits and improves dopaminergic functions in the rat hemi-Parkinson’s model. Sci. Rep. 8, 3973 (2018).
Fernandez-Del-Olmo, M. et al. Directed connectivity in Parkinson’s disease patients during over-ground and treadmill walking. Exp. Gerontol. 178, 112220 (2023).
Bougou, V. et al. Active and passive cycling decrease subthalamic β oscillations in Parkinson’s disease. Mov. Disord. 39, 85–93 (2024).
Gaßner, H. et al. Perturbation treadmill training improves clinical characteristics of gait and balance in Parkinson’s disease. J. Parkinsons Dis. 9, 413–426 (2019).
Hou, L. et al. Exercise-induced neuroprotection of the nigrostriatal dopamine system in Parkinson’s disease. Front. Aging Neurosci. 9, 358 (2017).
de Laat, B. et al. Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease. NPJ Parkinsons Dis. 10, 34 (2024).
Johansson, M. E. et al. Aerobic exercise alters brain function and structure in Parkinson’s disease: a randomized controlled trial. Ann. Neurol. 91, 203–216 (2022).
Sacheli, M. A. et al. Exercise increases caudate dopamine release and ventral striatal activation in Parkinson’s disease. Mov. Disord.34, 1891–1900 (2019).
Rotondo, R. et al. Dose-response effects of physical exercise standardized volume on peripheral biomarkers, clinical response, and brain connectivity in Parkinson’s disease: a prospective, observational, cohort study. Front. Neurol. 15, 1412311 (2024).
Jansen, A. E. et al. High intensity aerobic exercise improves bimanual coordination of grasping forces in Parkinson’s disease. Parkinsonism Relat. Disord. 87, 13–19 (2021).
Li, F. et al. Tai chi and postural stability in patients with Parkinson’s disease. N. Engl. J. Med. 366, 511–519 (2012).
Li, G. et al. Effect of long-term Tai Chi training on Parkinson’s disease: a 3.5-year follow-up cohort study. J. Neurol. Neurosurg. Psychiatry 95, 222–228 (2024).
Cristini, J. et al. The effects of exercise on sleep quality in persons with Parkinson’s disease: a systematic review with meta-analysis. Sleep. Med. Rev. 55, 101384 (2021).
Song, R. et al. The impact of Tai Chi and Qigong mind-body exercises on motor and non-motor function and quality of life in Parkinson’s disease: A systematic review and meta-analysis. Parkinsonism Relat. Disord. 41, 3–13 (2017).
Luo, K. et al. Effectiveness of Yijinjing on cognitive and motor functions in patients with Parkinson’s disease: study protocol for a randomized controlled trial. Front. Neurol. 15, 1357777 (2024).
Cherup, N. P. et al. Yoga meditation enhances proprioception and balance in individuals diagnosed with Parkinson’s disease. Percept. Mot. Skills 128, 304–323 (2021).
Duarte, J. D. S. et al. Physical activity based on dance movements as complementary therapy for Parkinson’s disease: effects on movement, executive functions, depressive symptoms, and quality of life. PLoS ONE 18, e0281204 (2023).
Ernst, M. et al. Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis. Cochrane Database Syst. Rev. 1, CD013856 (2023).
da Silva, P.G. et al. Neurotrophic factors in Parkinson’s disease are regulated by exercise: Evidence-based practice. J. Neurol. Sci. 363, 5–15 (2016).
Gamborg, M. et al. Parkinson’s disease and intensive exercise therapy – an updated systematic review and meta-analysis. Acta Neurol. Scand. 145, 504–528 (2022).
Uhrbrand, A. et al. Parkinson’s disease and intensive exercise therapy-a systematic review and meta-analysis of randomized controlled trials. J. Neurol. Sci. 353, 9–19 (2015).
Ben-Zeev, T., Shoenfeld, Y. & Hoffman, J. R. The effect of exercise on neurogenesis in the brain. Isr. Med. Assoc. J. IMAJ 24, 533–538 (2022).
Castro, S. L. et al. Blueberry juice augments exercise-induced neuroprotection in a Parkinson’s disease model through modulation of GDNF levels. IBRO Neurosci. Rep. 12, 217–227 (2022).
Castilla-Cortazar, I. et al. Is insulin-like growth factor-1 involved in Parkinson’s disease development? J. Transl. Med. 18, 70 (2020).
Stuckenschneider, T. et al. Disease-inclusive exercise classes improve physical fitness and reduce depressive symptoms in individuals with and without Parkinson’s disease-a feasibility study. Brain Behav. 11, e2352 (2021).
Chang, H.M. et al. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Hum. Reprod. Update 23, 1–18 (2016).
Goulding, S. R. et al. The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease. Neural Regen. Res. 15, 1432–1436 (2020).
Goulding, S. R. et al. Gene co-expression analysis of the human substantia nigra identifies BMP2 as a neurotrophic factor that can promote neurite growth in cells overexpressing wild-type or A53T α-synuclein. Parkinsonism Relat. Disord. 64, 194–201 (2019).
Hegarty, S. V., O’Keeffe, G. W. & Sullivan, A. M. BMP-Smad 1/5/8 signalling in the development of the nervous system. Prog. Neurobiol. 109, 28–41 (2013).
Terauchi, A. et al. The projection-specific signals that establish functionally segregated dopaminergic synapses. Cell 186, 3845–3861 (2023).
Kowianski, P. et al. BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol. Neurobiol. 38, 579–593 (2018).
Barreda Tomás, F.J. et al. BDNF Expression in Cortical GABAergic Interneurons. Int. J. Mol. Sci. 21, 1567 (2020).
Hirsch, M. A., Iyer, S. S. & Sanjak, M. Exercise-induced neuroplasticity in human Parkinson’s disease: what is the evidence telling us? Parkinsonism Relat. Disord. 22, S78–S81 (2016).
Paterno, A., Polsinelli, G. & Federico, B. Changes of brain-derived neurotrophic factor (BDNF) levels after different exercise protocols: a systematic review of clinical studies in Parkinson’s disease. Front. Physiol. 15, 1352305 (2024).
Bastioli, G. et al. Voluntary exercise boosts striatal dopamine release: evidence for the necessary and sufficient role of BDNF. J. Neurosci. 42, 4725–4736 (2022).
Brunelli, A. et al. Acute exercise modulates BDNF and pro-BDNF protein content in immune cells. Med. Sci. Sports Exerc. 44, 1871–1880 (2012).
Andreska, T. et al. Induction of BDNF expression in layer II/III and layer V neurons of the motor cortex is essential for motor learning. J. Neurosci.40, 6289–6308 (2020).
Campbell, T. S. et al. Early Life Stress Affects Bdnf Regulation: A Role for Exercise Interventions. Int. J. Mol. Sci. 23, 11729 (2022).
Wu, S.-Y. et al. Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway. Brain Behav. Immun. 25, 135–146 (2011).
Leem, Y.-H. et al. Neurogenic effects of rotarod walking exercise in subventricular zone, subgranular zone, and substantia nigra in MPTP-induced Parkinson’s disease mice. Sci. Rep. 12, 10544 (2022).
Wang, C. et al. Analgesic effect of exercise on neuropathic pain via regulating the complement component 3 of reactive astrocytes. Anesth. Analg. 139, 840–850 (2024).
Kelty, T. J. et al. Resistance-exercise training attenuates LPS-induced astrocyte remodeling and neuroinflammatory cytokine expression in female Wistar rats. J. Appl. Physiol. 132, 317–326 (2022).
Nakanishi, K. et al. Effect of low-intensity motor balance and coordination exercise on cognitive functions, hippocampal Abeta deposition, neuronal loss, neuroinflammation, and oxidative stress in a mouse model of Alzheimer’s disease. Exp. Neurol. 337, 113590 (2021).
Qiu, X. et al. C-reactive protein and risk of Parkinson’s disease: a systematic review and meta-analysis. Front. Neurol. 10, 384 (2019).
Tang, X. Q. et al. Retraction: aerobic exercise reverses the NF-kappaB/NLRP3 inflammasome/5-HT pathway by upregulating irisin to alleviate post-stroke depression. Ann. Transl. Med. 12, 128 (2024).
Yang, G. et al. Changes Observed in Potential Key Candidate Genes of Peripheral Immunity Induced by Tai Chi among Patients with Parkinsonas Disease. Genes 13, 1863 (2022).
Li, G. et al. Mechanisms of motor symptom improvement by long-term Tai Chi training in Parkinson’s disease patients. Transl. Neurodegener. 11, 6 (2022).
Leem, Y.-H. et al. Suppression of neuroinflammation and α-synuclein oligomerization by rotarod walking exercise in subacute MPTP model of Parkinson’s disease. Neurochem. Int. 165, 105519 (2023).
Jang, Y. et al. Neuroprotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson’s disease mice. Brain Res. 1655, 186–193 (2017).
Marino, G. et al. Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease restoring striatal synaptic plasticity. Sci. Adv. 9, eadh1403 (2023).
Wang, W. et al. Treadmill exercise alleviates neuronal damage by suppressing NLRP3 inflammasome and microglial activation in the MPTP mouse model of Parkinson’s disease. Brain Res. Bull. 174, 349–358 (2021).
Xu, J. et al. Voluntary exercise alleviates neural functional deficits in Parkinson’s disease mice by inhibiting microglial ferroptosis via SLC7A11/ALOX12 axis. NPJ Parkinsons Dis. 11, 55 (2025).
Eldeeb, M. A. et al. Mitochondrial quality control in health and in Parkinson’s disease. Physiol. Rev. 102, 1721–1755 (2022).
Pickrell, A. M. & Youle, R. J. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85, 257–273 (2015).
Henrich, M. T. et al. Mitochondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential. Mol. Neurodegener. 18, 83 (2023).
Zhang, S. et al. Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy. J. Cachexia Sarcopenia Muscle 14, 2126–2142 (2023).
Alcalá-Zúniga, D. et al. Enriched environment contributes to the recovery from neurotoxin-induced Parkinson’s disease pathology. Mol. Neurobiol. 61, 6734–6753 (2024).
Gan, Z. et al. Skeletal muscle mitochondrial remodeling in exercise and diseases. Cell Res. 28, 969–980 (2018).
Ludtmann, M. H. R. et al. α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease. Nat. Commun. 9, 2293 (2018).
Tung, Y.-T. et al. 10 weeks low intensity treadmill exercise intervention ameliorates motor deficits and sustains muscle mass via decreasing oxidative damage and increasing mitochondria function in a rat model of Parkinson’s disease. Life Sci. 350, 122733 (2024).
Koo, J. H. & Cho, J. Y. Erratum to: treadmill exercise attenuates alpha-synuclein levels by promoting mitochondrial function and autophagy possibly via SIRT1 in the chronic MPTP/P-induced mouse model of Parkinson’s disease. Neurotox. Res. 32, 532–533 (2017).
Rezaee, Z. et al. Effects of preventive treadmill exercise on the recovery of metabolic and mitochondrial factors in the 6-hydroxydopamine rat model of Parkinson’s disease. Neurotox. Res. 35, 908–917 (2019).
Zhou, L. et al. The Role of SIRT3 in Exercise and Aging. Cells 11, 2596 (2022).
Muñoz, A. et al. Physical exercise improves aging-related changes in angiotensin, IGF-1, SIRT1, SIRT3, and VEGF in the substantia nigra. J. Gerontol. A Biol. Sci. Med. Sci. 73, 1594–1601 (2018).
Koo, J.-H., Cho, J.-Y. & Lee, U.-B. Treadmill exercise alleviates motor deficits and improves mitochondrial import machinery in an MPTP-induced mouse model of Parkinson’s disease. Exp. Gerontol. 89, 20–29 (2017).
Jang, Y. et al. Modulation of mitochondrial phenotypes by endurance exercise contributes to neuroprotection against a MPTP-induced animal model of PD. Life Sci. 209, 455–465 (2018).
Hwang, D.-J. et al. Neuroprotective effect of treadmill exercise possibly via regulation of lysosomal degradation molecules in mice with pharmacologically induced Parkinson’s disease. J. Physiol. Sci.68, 707–716 (2018).
Kelly, N. A. et al. Novel, high-intensity exercise prescription improves muscle mass, mitochondrial function, and physical capacity in individuals with Parkinson’s disease. J. Appl. Physiol.116, 582–592 (2014).
Zhang, X. et al. Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease. NPJ Parkinsons Dis. 9, 13 (2023).
Kam, T.-I. et al. Amelioration of pathologic α-synuclein-induced Parkinson’s disease by irisin. Proc. Natl. Acad. Sci. USA 119, e2204835119 (2022).
Dutta, D. et al. Treadmill exercise reduces alpha-synuclein spreading via PPARalpha. Cell Rep. 40, 111058 (2022).
Bao, J.-F. et al. Irisin, a fascinating field in our times. Trends Endocrinol. Metab. TEM 33, 601–613 (2022).
Zhao, R. et al. Role of irisin in bone diseases. Front. Endocrinol. 14, 1212892 (2023).
Peng, J. & Wu, J. Effects of the FNDC5/irisin on elderly dementia and cognitive impairment. Front. Aging Neurosci. 14, 863901 (2022).
Dicarlo, M. et al. Irisin levels in cerebrospinal fluid correlate with biomarkers and clinical dementia scores in Alzheimer disease. Ann. Neurol. 96, 61–73 (2024).
Zhang, H. et al. Irisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process. Ageing Res. Rev. 80, 101680 (2022).
Sun, B. et al. Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-β/Smad signaling in a growing mouse model of osteogenesis imperfecta. J. Orthop. Translat. 38, 175–189 (2023).
Guo, P. et al. Irisin rescues blood-brain barrier permeability following traumatic brain injury and contributes to the neuroprotection of exercise in traumatic brain injury. Oxid. Med. Cell. Longev. 2021, 1118981 (2021).
Sadier, N. S. et al. Irisin: An unveiled bridge between physical exercise and a healthy brain. Life Sci. 339, 122393 (2024).
Wagner, C. A. et al. Translational research on cognitive impairment in chronic kidney disease. Nephrol. Dialysis Transplant. 40, 621–631 (2025).
Wang, Y. et al. Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin alphaVbeta5/AMPK signaling pathway after intracerebral hemorrhage in mice. J. Neuroinflammation 19, 82 (2022).
Mao, M. Z. et al. FNDC5/irisin-enriched sEVs conjugated with bone-targeting aptamer alleviate osteoporosis: a potential alternative to exercise. J. Nanobiotechnology 23, 504 (2025).
Shi, X. et al. Relationship of irisin with disease severity and dopamine uptake in Parkinson’s disease patients. Neuroimage Clin. 41, 103555 (2024).
Li, D.-J. et al. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia. Metab. Clin. Exp. 68, 31–42 (2017).
Qiu, R. et al. Irisin’s emerging role in Parkinson’s disease research: a review from molecular mechanisms to therapeutic prospects. Life Sci. 357, 123088 (2024).
Choi, J.-W. et al. Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation. Redox Biol. 71, 103101 (2024).
Zhu, M. et al. Irisin promotes autophagy and attenuates NLRP3 inflammasome activation in Parkinson’s disease. Int. Immunopharmacol. 149, 114201 (2025).
Raefsky, S. M. & Mattson, M. P. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance. Free Radic. Biol. Med. 102, 203–216 (2017).
Valenzuela, P. L. et al. Exercise benefits on Alzheimer’s disease: state-of-the-science. Ageing Res. Rev. 62, 101108 (2020).
Liu, Y. et al. The neuroprotective effect of irisin in ischemic stroke. Front. Aging Neurosci. 12, 588958 (2020).
Lourenco, M. V. et al. Irisin stimulates protective signaling pathways in rat hippocampal neurons. Front. Cell. Neurosci. 16, 953991 (2022).
Leger, C. et al. Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin. Int. J. Mol. Sci. 25, 1213 (2024).
Boström, P. et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468 (2012).
Jedrychowski, M. P. et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 22, 734–740 (2015).
Tsuchiya, Y. et al. Resistance exercise induces a greater irisin response than endurance exercise. Metab. Clin. Exp. 64, 1042–1050 (2015).
Anastasilakis, A. D. et al. Circulating irisin in healthy, young individuals: day-night rhythm, effects of food intake and exercise, and associations with gender, physical activity, diet, and body composition. J. Clin. Endocrinol. Metab. 99, 3247–3255 (2014).
Guo, M. et al. BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise. J. Sport Health Sci. 14, 100968 (2024).
Nowell, J. et al. Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease. Ageing Res. Rev. 89, 101979 (2023).
Sun, Y. et al. Irisin delays the onset of type 1 diabetes in NOD mice by enhancing intestinal barrier. Int. J. Biol. Macromol. 265, 130857 (2024). (Pt 1).
Islam, M. R. et al. Exercise hormone irisin is a critical regulator of cognitive function. Nat. Metab. 3, 1058–1070 (2021).
Shin, M. S. et al. Treadmill exercise facilitates synaptic plasticity on dopaminergic neurons and fibers in the mouse model with Parkinson’s disease. Neurosci. Lett. 621, 28–33 (2016).
Fathalla, A. M. et al. Adenosine A2A receptor blockade prevents rotenone-induced motor impairment in a rat model of Parkinsonism. Front. Behav. Neurosci. 10, 35 (2016).
Viana, S. D. et al. The effects of physical exercise on nonmotor symptoms and on neuroimmune RAGE network in experimental Parkinsonism. J. Appl. Physiol.123, 161–171 (2017).
Li, R. et al. Exercise attenuates neuronal degeneration in Parkinson’s disease rat model by regulating the level of adenosine 2A receptor. Folia Neuropathol.61, 217–223 (2023).
Liu, W. et al. Regular aerobic exercise-alleviated dysregulation of CAMKIIα carbonylation to mitigate Parkinsonism via homeostasis of apoptosis with autophagy. J. Neuropathol. Exp. Neurol. 79, 46–61 (2020).
Shen, J. et al. Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases. Front. Physiol. 15, 1337442 (2024).
Fischetti, F. et al. The role of exercise parameters on small extracellular vesicles and microRNAs cargo in preventing neurodegenerative diseases. Front. Physiol. 14, 1241010 (2023).
Goulding, S. R. et al. Growth differentiation factor 5: a neurotrophic factor with neuroprotective potential in Parkinson’s disease. Neural Regen. Res. 17, 38–44 (2022).
Fukuchi, M. et al. Visualizing changes in brain-derived neurotrophic factor (BDNF) expression using bioluminescence imaging in living mice. Sci. Rep. 7, 4949 (2017).
Rodrigues, ÉF. et al. Challenges in recombinant brain-derived neurotrophic factor production. Trends Biotechnol. 42, 522–525 (2024).
Allen, S. J. et al. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol. Ther.138, 155–175 (2013).
Wang, J. et al. Irisin protects against sepsis-associated encephalopathy by suppressing ferroptosis via activation of the Nrf2/GPX4 signal axis. Free Radic. Biol. Med. 187, 171–184 (2022).
Xu, X. et al. Irisin prevents hypoxic-ischemic brain damage in rats by inhibiting oxidative stress and protecting the blood-brain barrier. Peptides 161, 170945 (2023).
Guo, P. et al. Effects of irisin on the dysfunction of blood-brain barrier in rats after focal cerebral ischemia/reperfusion. Brain Behav. 9, e01425 (2019).
Dehghan, F. et al. Irisin injection mimics exercise effects on the brain proteome. Eur. J. Neurosci. 54, 7422–7441 (2021).
Guo, M. et al. Irisin ameliorates age-associated sarcopenia and metabolic dysfunction. J. Cachexia Sarcopenia Muscle 14, 391–405 (2023).
Zhao, R. et al. Aerobic Exercise Restores Hippocampal Neurogenesis and Cognitive Function by Decreasing Microglia Inflammasome Formation Through Irisin/NLRP3 Pathway. Aging Cell 24, e70061 (2025).
Gonçalves, R. A. & De Felice, F. G. The crosstalk between brain and periphery: implications for brain health and disease. Neuropharmacology 197, 108728 (2021).
Khalil, M.H. et al. The Impact of Walking on BDNF as a Biomarker of Neuroplasticity: A Systematic Review. Brain Sci. 15, 254 (2025).
Zigmond, M. J. et al. Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. Parkinsonism Relat. Disord. 15, S42–S45 (2009).
Harvey, B. K., Hoffer, B. J. & Wang, Y. Stroke and TGF-beta proteins: glial cell line-derived neurotrophic factor and bone morphogenetic protein. Pharmacol. Ther.105, 113–125 (2005).
Traor‚ M. et al. An embryonic CaVá1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse. Sci. Transl. Med. 11, eaaw1131 (2019).