The role of physical activity in prevention of neurodegenerative diseases via irisin synthesis – a contemporary review
DOI:
https://doi.org/10.12775/JEHS.2026.89.69878Keywords
irisin, FNDC5, neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, physical activity, BDNF, muscle–brain axisAbstract
Background:
Neurodegenerative diseases pose as a growing challenge due to population aging and the lack of causal therapies. Shared pathological mechanisms include oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Regular physical activity shows neuroprotective effects, and irisin—an exercise-induced myokine generated by proteolytic cleavage of FNDC5 under PGC-1α control—may be an important mediator of the muscle–brain axis.
Aim:
To present the current state of knowledge on irisin, with particular emphasis on its role in the pathogenesis, diagnosis, and potential treatment of neurodegenerative diseases.
Material and methods:
This narrative review summarizes available evidence on the biological properties of irisin, its proposed mechanisms of action and its effects on energy metabolism, inflammation, oxidative stress, and neuroplasticity in the context of NDDs.
Results:
Experimental studies indicate that irisin increases hippocampal BDNF expression, promotes neurogenesis and synaptic plasticity, and reduces neuronal apoptosis. In Alzheimer’s disease models, FNDC5/irisin levels were reduced in the hippocampus and cerebrospinal fluid, whereas increasing FNDC5/irisin improved memory and attenuated amyloid-related pathology. In Parkinson’s disease models, irisin reduced α-synuclein aggregation, protected dopaminergic neurons, and improved motor performance. In ALS, irisin has been proposed to modulate oxidative stress and neuroinflammation through NRF2 activation and NF-κB inhibition, although clinical evidence remains limited.
Conclusions:
Irisin is a promising biomarker and potential therapeutic target in neurodegenerative diseases. Despite encouraging preclinical results, clinical translation requires well-designed human studies. At present, regular physical activity remains the most practical strategy to modulate endogenous irisin levels and may support prevention and management of NDDs.
References
1. Williams A. Defining neurodegenerative diseases. BMJ. 2002;324(7352):1465–1466. https://doi.org/10.1136/bmj.324.7352.1465
2. Ricci C. Neurodegenerative disease: from molecular basis to therapy, 2nd edition. Int J Mol Sci. 2025;26(5):1929. https://doi.org/10.3390/ijms26051929
3. Checkoway H, Lundin JI, Kelada SN. Neurodegenerative diseases. IARC Sci Publ. 2011;(163):407–419.
4. Veronese, N., Nova, A., Fazia, T., Riggi, E., Yang, L., Piccio, L., Huang, B. H., Ahmadi, M., Barbagallo, M., Notarnicola, M., Giannelli, G., De Pergola, G., Stamatakis, E., Cereda, E., Bernardinelli, L., & Fontana, L. (2024). Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society, 39(7), 1203–1212. https://doi.org/10.1002/mds.29778
5. Heemels MT. Neurodegenerative diseases. Nature. 2016;539(7628):179. https://doi.org/10.1038/539179a
6. Di Liegro CM, Schiera G, Proia P, Di Liegro I. Physical activity and brain health. Genes (Basel). 2019;10(9):720. https://doi.org/10.3390/genes10090720
7. Bonanni, R., Cariati, I., Tarantino, U., D'Arcangelo, G., & Tancredi, V. (2022). Physical Exercise and Health: A Focus on Its Protective Role in Neurodegenerative Diseases. Journal of functional morphology and kinesiology, 7(2), 38. https://doi.org/10.3390/jfmk7020038
8. Liu, Y., Yan, T., Chu, J. M., Chen, Y., Dunnett, S., Ho, Y. S., Wong, G. T., & Chang, R. C. (2019). The beneficial effects of physical exercise in the brain and related pathophysiological mechanisms in neurodegenerative diseases. Laboratory investigation; a journal of technical methods and pathology, 99(7), 943–957. https://doi.org/10.1038/s41374-019-0232-y
9. Huang, L. Y., Ou, Y. N., Yang, Y. X., Wang, Z. T., Tan, L., & Yu, J. T. (2023). Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study. Translational psychiatry, 13(1), 267. https://doi.org/10.1038/s41398-023-02553-9
10. Vints WAJ, Gökçe E, Langeard A, et al. Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis. Front Aging Neurosci. 2023;15:1213057. https://doi.org/10.3389/fnagi.2023.1213057
11. Oudbier SJ, Goh J, Looijaard SMLM, et al. Pathophysiological mechanisms explaining the association between low skeletal muscle mass and cognitive function. J Gerontol A Biol Sci Med Sci. 2022;77(10):1959–1968. https://doi.org/10.1093/gerona/glac121
12. Küster OC, Laptinskaya D, Fissler P, et al. Novel blood-based biomarkers of cognition, stress, and physical or cognitive training in older adults at risk of dementia. J Alzheimers Dis. 2017;59(3):1097–1111. https://doi.org/10.3233/JAD-170447
13. Zhang Y, Zhang X, Lin S. Irisin: a bridge between exercise and neurological diseases. Heliyon. 2022;8(12):e12352. https://doi.org/10.1016/j.heliyon.2022.e12352
14. Ferrer-Martínez, A., Ruiz-Lozano, P., & Chien, K. R. (2002). Mouse PeP: a novel peroxisomal protein linked to myoblast differentiation and development. Developmental dynamics : an official publication of the American Association of Anatomists, 224(2), 154–167. https://doi.org/10.1002/dvdy.10099
15. Teufel, A., Malik, N., Mukhopadhyay, M., & Westphal, H. (2002). Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes. Gene, 297(1-2), 79–83. https://doi.org/10.1016/s0378-1119(02)00828-4
16. Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–468. https://doi.org/10.1038/nature10777
17. Aydin S, Kuloglu T, Aydin S, et al. A comprehensive immunohistochemical examination of the distribution of the fat-burning protein irisin in biological tissues. Peptides. 2014;61:130–136. https://doi.org/10.1016/j.peptides.2014.09.014
18. Flori L, Testai L, Calderone V. The “irisin system”: from biological roles to pharmacological and nutraceutical perspectives. Life Sci. 2021;267:118954. https://doi.org/10.1016/j.lfs.2020.118954
19. Jedrychowski MP, Wrann CD, Paulo JA, et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 2015;22(4):734–740. https://doi.org/10.1016/j.cmet.2015.08.001
20. Lee P, Linderman JD, Smith S, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014;19(2):302–309. https://doi.org/10.1016/j.cmet.2013.12.017
21. Roca-Rivada A, Castelao C, Senin LL, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013;8(4):e60563. https://doi.org/10.1371/journal.pone.0060563
22. Wang YT, Zheng SY, Jiang SD, et al. Irisin in degenerative musculoskeletal diseases: functions in system and potential in therapy. Pharmacol Res. 2024;210:107480. https://doi.org/10.1016/j.phrs.2024.107480
23. Lourenco MV, Frozza RL, de Freitas GB, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models. Nat Med. 2019;25(1):165–175. https://doi.org/10.1038/s41591-018-0275-4
24. Kim H, Wrann CD, Jedrychowski M, et al. Irisin mediates effects on bone and fat via αV integrin receptors. Cell. 2018;175(7):1756–1768.e17. https://doi.org/10.1016/j.cell.2018.10.025
25. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673–687. https://doi.org/10.1016/S0092-8674(02)00971-6
26. Rabiee F, Lachinani L, Ghaedi S, et al. New insights into the cellular activities of FNDC5/irisin and its signaling pathways. Cell Biosci. 2020;10:51. https://doi.org/10.1186/s13578-020-00413-3
27. Shi H, Hao X, Sun Y, et al. Exercise-inducible circulating extracellular vesicle irisin promotes browning and the thermogenic program in white adipose tissue. Acta Physiol (Oxf). 2024;240(1):e14103. https://doi.org/10.1111/apha.14103
28. Slate-Romano JJ, Yano N, Zhao TC. Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome. Mol Cell Endocrinol. 2022;552:111676. https://doi.org/10.1016/j.mce.2022.111676
29. Mazur-Bialy AI, Pocheć E, Zarawski M. Anti-inflammatory properties of irisin, mediator of physical activity, are connected with TLR4/MyD88 signaling pathway activation. Int J Mol Sci. 2017;18(4):701. https://doi.org/10.3390/ijms18040701
30. de Oliveira Bristot VJ, de Bem Alves AC, Cardoso LR, et al. The role of PGC-1α/UCP2 signaling in the beneficial effects of physical exercise on the brain. Front Neurosci. 2019;13:292. https://doi.org/10.3389/fnins.2019.00292
31. Kornel A, den Hartogh DJ, Klentrou P, Tsiani E. Role of the myokine irisin on bone homeostasis: review of the current evidence. Int J Mol Sci. 2021;22(17):9136. https://doi.org/10.3390/ijms22179136
32. Polyzos SA, Anastasilakis AD, Efstathiadou ZA, et al. Irisin in metabolic diseases. Endocrine. 2018;59(2):260–274. https://doi.org/10.1007/s12020-017-1476-1
33. Colaianni G, Cuscito C, Mongelli T, et al. The myokine irisin increases cortical bone mass. Proc Natl Acad Sci U S A. 2015;112(39):12157–12162. https://doi.org/10.1073/pnas.1516622112
34. Liu C, Wei A, Wang T. Irisin, an effective treatment for cardiovascular diseases? J Cardiovasc Dev Dis. 2022;9(9):305. https://doi.org/10.3390/jcdd9090305
35. Wrann CD, White JP, Salogiannis J, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab.2013;18(5):649–659. https://doi.org/10.1016/j.cmet.2013.09.008
36. Korta P, Pocheć E, Mazur-Biały A. Irisin as a multifunctional protein: implications for health and certain diseases. Medicina (Kaunas). 2019;55(8):485. https://doi.org/10.3390/medicina55080485
37. Moon HS, Dincer F, Mantzoros CS. Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis. Metabolism. 2013;62(8):1131–1136. https://doi.org/10.1016/j.metabol.2013.04.007
38. Qi JY, Yang LK, Wang XS, et al. Irisin: a promising treatment for neurodegenerative diseases. Neuroscience. 2022;498:289–299. https://doi.org/10.1016/j.neuroscience.2022.07.018
39. Pesce M, Ballerini P, Paolucci T, et al. Irisin and autophagy: first update. Int J Mol Sci. 2020;21(20):7587. https://doi.org/10.3390/ijms21207587
40. Jin Z, Guo P, Li X, et al. Neuroprotective effects of irisin against cerebral ischemia/reperfusion injury via Notch signaling pathway. Biomed Pharmacother. 2019;120:109452. https://doi.org/10.1016/j.biopha.2019.109452
41. Li DJ, Li YH, Yuan HB, et al. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways. Metabolism. 2017;68:31–42. https://doi.org/10.1016/j.metabol.2016.12.003
42. Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–1590. https://doi.org/10.1016/S0140-6736(20)32205-4
43. Cattaneo C, Jost WH. Pain in Parkinson's disease: pathophysiology, classification and treatment. J Integr Neurosci. 2023;22(5):132. https://doi.org/10.31083/j.jin2205132
44. Day JO, Mullin S. The genetics of Parkinson’s disease and implications for clinical practice. Genes (Basel). 2021;12(7):1006. https://doi.org/10.3390/genes12071006
45. Eisen A, Vucic S, Mitsumoto H. History of ALS and the competing theories on pathogenesis. Clin Neurophysiol Pract. 2023;9:1–12. https://doi.org/10.1016/j.cnp.2023.11.004
46. Teleanu DM, Niculescu AG, Lungu II, et al. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases. Int J Mol Sci. 2022;23(11):5938. https://doi.org/10.3390/ijms23115938
47. Zhang XX, Tian Y, Wang ZT, et al. The epidemiology of Alzheimer’s disease modifiable risk factors and prevention. J Prev Alzheimers Dis. 2021;8(3):313–321. https://doi.org/10.14283/jpad.2021.15
48. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19(4):1598–1695. https://doi.org/10.1002/alz.13016
49. Quinn, L.S., Anderson, B.G., Conner, J.D. et al. Circulating irisin levels and muscle FNDC5 mRNA expression are independent of IL-15 levels in mice. Endocrine 50, 368–377 (2015). https://doi.org/10.1007/s12020-015-0607-9
50. Piya, M. K., Harte, A. L., Sivakumar, K., Tripathi, G., Voyias, P. D., James, S., Sabico, S., Al-Daghri, N. M., Saravanan, P., Barber, T. M., Kumar, S., Vatish, M., & McTernan, P. G. (2014). The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. American journal of physiology. Endocrinology and metabolism, 306(5), E512–E518. https://doi.org/10.1152/ajpendo.00308.2013
51. Phillips, C., Baktir, M. A., Srivatsan, M., & Salehi, A. (2014). Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Frontiers in cellular neuroscience, 8, 170. https://doi.org/10.3389/fncel.2014.00170
52. Lourenco, M. V., Frozza, R. L., de Freitas, G. B., Zhang, H., Kincheski, G. C., Ribeiro, F. C., Gonçalves, R. A., Clarke, J. R., Beckman, D., Staniszewski, A., Berman, H., Guerra, L. A., Forny-Germano, L., Meier, S., Wilcock, D. M., de Souza, J. M., Alves-Leon, S., Prado, V. F., Prado, M. A. M., Abisambra, J. F., … De Felice, F. G. (2019). Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models. Nature medicine, 25(1), 165–175. https://doi.org/10.1038/s41591-018-0275-4
53. Hashemi, M. S., Ghaedi, K., Salamian, A., Karbalaie, K., Emadi-Baygi, M., Tanhaei, S., Nasr-Esfahani, M. H., & Baharvand, H. (2013). Fndc5 knockdown significantly decreased neural differentiation rate of mouse embryonic stem cells. Neuroscience, 231, 296–304. https://doi.org/10.1016/j.neuroscience.2012.11.041
54. Moon, H. S., Dincer, F., & Mantzoros, C. S. (2013). Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines. Metabolism: clinical and experimental, 62(8), 1131–1136. https://doi.org/10.1016/j.metabol.2013.04.007
55. Li, D. J., Li, Y. H., Yuan, H. B., Qu, L. F., & Wang, P. (2017). 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. Metabolism: clinical and experimental, 68, 31–42. https://doi.org/10.1016/j.metabol.2016.12.003
56. Jackson, T.C., Gorse, K., Herrmann, J.R. et al. Hippocampal and Prefrontal Cortical Brain Tissue Levels of Irisin and GDF15 Receptor Subunits in Children. Mol Neurobiol 58, 2145–2157 (2021). https://doi.org/10.1007/s12035-020-02250-4
57. Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Jr, Losón, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C., & Shaw, R. J. (2016). Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science (New York, N.Y.), 351(6270), 275–281. https://doi.org/10.1126/science.aab4138
58. Zhang, W., Chang, L., Zhang, C., Zhang, R., Li, Z., Chai, B., Li, J., Chen, E., & Mulholland, M. (2015). Irisin: A myokine with locomotor activity. Neuroscience letters, 595, 7–11. https://doi.org/10.1016/j.neulet.2015.03.069
59. Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell metabolism, 18(5), 649–659. https://doi.org/10.1016/j.cmet.2013.09.008
60. Diniz, B. S., & Teixeira, A. L. (2011). Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond. Neuromolecular medicine, 13(4), 217–222. https://doi.org/10.1007/s12017-011-8154-x
61. Arancibia, S., Silhol, M., Moulière, F., Meffre, J., Höllinger, I., Maurice, T., & Tapia-Arancibia, L. (2008). Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiology of disease, 31(3), 316–326. https://doi.org/10.1016/j.nbd.2008.05.012
62. Guillin, O., Griffon, N., Bezard, E., Leriche, L., Diaz, J., Gross, C., & Sokoloff, P. (2003). Brain-derived neurotrophic factor controls dopamine D3 receptor expression: therapeutic implications in Parkinson's disease. European journal of pharmacology, 480(1-3), 89–95. https://doi.org/10.1016/j.ejphar.2003.08.096
63. Camandola, S., & Mattson, M. P. (2017). Brain metabolism in health, aging, and neurodegeneration. The EMBO journal, 36(11), 1474–1492. https://doi.org/10.15252/embj.201695810
64. Yan, Q. S., Feng, M. J., & Yan, S. E. (2005). Different expression of brain-derived neurotrophic factor in the nucleus accumbens of alcohol-preferring (P) and -nonpreferring (NP) rats. Brain research, 1035(2), 215–218. https://doi.org/10.1016/j.brainres.2004.12.039
65. Lee, J., Duan, W., & Mattson, M. P. (2002). Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. Journal of neurochemistry, 82(6), 1367–1375. https://doi.org/10.1046/j.1471-4159.2002.01085.x
66. Zsuga, J., Tajti, G., Papp, C., Juhasz, B., & Gesztelyi, R. (2016). FNDC5/irisin, a molecular target for boosting reward-related learning and motivation. Medical hypotheses, 90, 23–28. https://doi.org/10.1016/j.mehy.2016.02.020
67. Chen, Z. Y., Cao, L., Wang, L. M., Guo, C., Ye, J. L., Chai, Y. F., & Yan, Z. Y. (2001). Development of neurotrophic molecules for treatment of neurodegeneration. Current protein & peptide science, 2(3), 261–276. https://doi.org/10.2174/1389203013381125
68. Liu, P., Zou, D., Yi, L., Chen, M., Gao, Y., Zhou, R., Zhang, Q., Zhou, Y., Zhu, J., Chen, K., & Mi, M. (2015). Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1α pathway. Restorative neurology and neuroscience, 33(2), 143–157. https://doi.org/10.3233/RNN-140446
69. Nagahara, A. H., Merrill, D. A., Coppola, G., Tsukada, S., Schroeder, B. E., Shaked, G. M., Wang, L., Blesch, A., Kim, A., Conner, J. M., Rockenstein, E., Chao, M. V., Koo, E. H., Geschwind, D., Masliah, E., Chiba, A. A., & Tuszynski, M. H. (2009). Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nature medicine, 15(3), 331–337. https://doi.org/10.1038/nm.1912
70. Longo, F. M., Yang, T., Knowles, J. K., Xie, Y., Moore, L. A., & Massa, S. M. (2007). Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms. Current Alzheimer research, 4(5), 503–506. https://doi.org/10.2174/156720507783018316
71. Jedrychowski, M. P., Wrann, C. D., Paulo, J. A., Gerber, K. K., Szpyt, J., Robinson, M. M., Nair, K. S., Gygi, S. P., & Spiegelman, B. M. (2015). Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry. Cell metabolism, 22(4), 734–740. https://doi.org/10.1016/j.cmet.2015.08.001
72. De la Rosa, A., Olaso-Gonzalez, G., Arc-Chagnaud, C., Millan, F., Salvador-Pascual, A., García-Lucerga, C., Blasco-Lafarga, C., Garcia-Dominguez, E., Carretero, A., Correas, A. G., Viña, J., & Gomez-Cabrera, M. C. (2020). Physical exercise in the prevention and treatment of Alzheimer's disease. Journal of sport and health science, 9(5), 394–404. https://doi.org/10.1016/j.jshs.2020.01.004
73. Puig, K. L., Floden, A. M., Adhikari, R., Golovko, M. Y., & Combs, C. K. (2012). Amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity. PloS one, 7(1), e30378. https://doi.org/10.1371/journal.pone.0030378
74. Zhang, T., Pan, B. S., Zhao, B., Zhang, L. M., Huang, Y. L., & Sun, F. Y. (2009). Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of beta-secretase activation and beta-amyloid generation in rat brains. Neuroscience, 161(4), 1045–1056. https://doi.org/10.1016/j.neuroscience.2009.04.032
75. Droogsma, E., van Asselt, D., Bieze, H., Veeger, N., & De Deyn, P. P. (2015). The relationship of weight change trajectory with medial temporal lobe atrophy in patients with mild Alzheimer's disease: results from a cohort study. Alzheimer's research & therapy, 7(1), 18. https://doi.org/10.1186/s13195-015-0098-1
76. Park, K. H., Zaichenko, L., Peter, P., Davis, C. R., Crowell, J. A., & Mantzoros, C. S. (2014). Diet quality is associated with circulating C-reactive protein but not irisin levels in humans. Metabolism: clinical and experimental, 63(2), 233–241. https://doi.org/10.1016/j.metabol.2013.10.011
77. Choi, Y. K., Kim, M. K., Bae, K. H., Seo, H. A., Jeong, J. Y., Lee, W. K., Kim, J. G., Lee, I. K., & Park, K. G. (2013). Serum irisin levels in new-onset type 2 diabetes. Diabetes research and clinical practice, 100(1), 96–101. https://doi.org/10.1016/j.diabres.2013.01.007
78. Xiong, X. Q., Chen, D., Sun, H. J., Ding, L., Wang, J. J., Chen, Q., Li, Y. H., Zhou, Y. B., Han, Y., Zhang, F., Gao, X. Y., Kang, Y. M., & Zhu, G. Q. (2015). FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity. Biochimica et biophysica acta, 1852(9), 1867–1875. https://doi.org/10.1016/j.bbadis.2015.06.017
79. GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis. Lancet Neurol. 2018;17(11):939–953. https://doi.org/10.1016/S1474-4422(18)30295-3
80. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021;20(5):385–397. https://doi.org/10.1016/S1474-4422(21)00030-2
81. Johansson, M. E., Cameron, I. G. M., Van der Kolk, N. M., de Vries, N. M., Klimars, E., Toni, I., Bloem, B. R., & Helmich, R. C. (2022). Aerobic Exercise Alters Brain Function and Structure in Parkinson's Disease: A Randomized Controlled Trial. Annals of neurology, 91(2), 203–216. https://doi.org/10.1002/ana.26291
82. Tsukita, K., Sakamaki-Tsukita, H., & Takahashi, R. (2022). Long-term Effect of Regular Physical Activity and Exercise Habits in Patients With Early Parkinson Disease. Neurology, 98(8), e859–e871. https://doi.org/10.1212/WNL.0000000000013218
83. Kam TI, Park H, Chou SC, et al. Amelioration of pathologic alpha-synuclein-induced Parkinson's disease by irisin. Proc Natl Acad Sci U S A. 2022;119(36):e2204835119. https://doi.org/10.1073/pnas.2204835119
84. Zarbakhsh, S., Safari, M., Aldaghi, M. R., Sameni, H. R., Ghahari, L., Khaleghi Lagmouj, Y., Rahimi Jaberi, K., & Parsaie, H. (2019). Irisin protects the substantia nigra dopaminergic neurons in the rat model of Parkinson's disease. Iranian journal of basic medical sciences, 22(7), 722–728. https://doi.org/10.22038/ijbms.2019.33444.7987
85. Shi X, Gu Q, Fu C, et al. Relationship of irisin with disease severity and dopamine uptake in Parkinson's disease. Neuroimage Clin. 2024;41:103555. https://doi.org/10.1016/j.nicl.2023.103555
86. Xu, X., He, X., Ma, S., Li, M., & Huang, Q. (2021). Nurr1 downregulation is caused by CREB inactivation in a Parkinson's disease mouse model. Neuroscience letters, 759, 136045. https://doi.org/10.1016/j.neulet.2021.136045
87. Zhu, M., Peng, Q., Li, S., Zhang, G., & Zhang, Z. (2025). Irisin promotes autophagy and attenuates NLRP3 inflammasome activation in Parkinson's disease. International immunopharmacology, 149, 114201. https://doi.org/10.1016/j.intimp.2025.114201
88. Kwon, H.S., Koh, SH. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener 9, 42 (2020). https://doi.org/10.1186/s40035-020-00221-2
89. Bayer H, Lang K, Buck E, et al. ALS-causing mutations affect PGC-1α expression. Neurobiol Dis. 2017;97(Pt A):36–45. https://doi.org/10.1016/j.nbd.2016.11.001
90. Petri S, Körner S, Kiaei M. Nrf2/ARE signaling pathway in ALS. Neurol Res Int. 2012;2012:878030. https://doi.org/10.1155/2012/878030
91. Lunetta C, Lizio A, Tremolizzo L, et al. Serum irisin in ALS patients. J Neurol. 2018;265(12):3001–3008. https://doi.org/10.1007/s00415-018-9093-3
92. Pignataro, P., Dicarlo, M., Zerlotin, R., Zecca, C., Dell'Abate, M. T., Buccoliero, C., Logroscino, G., Colucci, S., & Grano, M. (2021). FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective. International journal of molecular sciences, 22(4), 1605. https://doi.org/10.3390/ijms22041605
93. Young, M. F., Valaris, S., & Wrann, C. D. (2019). A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases. Progress in cardiovascular diseases, 62(2), 172–178. https://doi.org/10.1016/j.pcad.2019.02.007
94. Nygaard H, Slettaløkken G, Vegge G, et al. Irisin in blood increases transiently after single sessions of intense endurance exercise and heavy strength training. PLoS One. 2015;10(3):e0121367. https://doi.org/10.1371/journal.pone.0121367
95. Daskalopoulou SS, Cooke AB, Gomez YH, et al. Plasma irisin levels progressively increase in response to increasing exercise workloads. Eur J Endocrinol. 2014;171(3):343–352. https://doi.org/10.1530/EJE-14-0204
96. Torabi, A., Reisi, J., Kargarfard, M., & Mansourian, M. (2024). Differences in the Impact of Various Types of Exercise on Irisin Levels: A Systematic Review and Meta-Analysis. International journal of preventive medicine, 15, 11. https://doi.org/10.4103/ijpvm.ijpvm_76_23
97. Huh, J. Y., Panagiotou, G., Mougios, V., Brinkoetter, M., Vamvini, M. T., Schneider, B. E., & Mantzoros, C. S. (2012). FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism: clinical and experimental, 61(12), 1725–1738. https://doi.org/10.1016/j.metabol.2012.09.002
98. Cosio, P. L., Pelaez, M., Cadefau, J. A., & Farran-Codina, A. (2023). Systematic Review and Meta-Analysis of Circulating Irisin Levels Following Endurance Training: Results of Continuous and Interval Training. Biological research for nursing, 25(3), 367–381. https://doi.org/10.1177/10998004221142580
99. Muzaffar S, Tyagi A, Pugazhenthi S. Therapeutic Potential of Irisin in Neurodegenerative Diseases. International Journal of Molecular Sciences. 2025; 26(23):11348. https://doi.org/10.3390/ijms262311348
100. Minuti, A., Raffaele, I., Scuruchi, M., Lui, M., Muscarà, C., & Calabrò, M. (2025). Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases. Antioxidants (Basel, Switzerland), 14(5), 554. https://doi.org/10.3390/antiox14050554
101. Bretland, K. A., Lin, L., Bretland, K. M., Smith, M. A., Fleming, S. M., & Dengler-Crish, C. M. (2021). Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice. Neuropathology and applied neurobiology, 47(7), 967–978. https://doi.org/10.1111/nan.12711
102. Wang, C., Wang, X., Sun, S., Chang, Y., Lian, P., Guo, H., Zheng, S., Ma, R., & Li, G. (2024). Irisin inhibits microglial senescence via TFAM-mediated mitochondrial metabolism in a mouse model of tauopathy. Immunity & ageing : I & A, 21(1), 30. https://doi.org/10.1186/s12979-024-00437-0
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Izabela Grzyb, Katarzyna Łysynkiewicz, Jan Szewczyk, Zuzanna Wątek, Alicja Smolińska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 2
Number of citations: 0
