{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:59:24Z","timestamp":1793073564224,"version":"4.5.0"},"reference-count":114,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Inter-organ communication plays a vital role in the pathogenesis of neurodegenerative diseases (ND), including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Emerging research highlights the involvement of the gut\u2013brain axis, immune system, and peripheral metabolic systems in modulating neuroinflammation, protein misfolding, and neuronal dysfunction by releasing cytokines, adipokines, growth factors, and other soluble factors, which in turn affect neuronal health and systemic inflammation. This review explores the complex bidirectional interactions between the brain and peripheral organs, including the gut, adipose tissue, liver, muscle, bone and immune system. Notably, the gut microbiome\u2019s role in neurodegenerative diseases through the gut\u2013brain axis, the impact of adipose tissue in inflammation and metabolic regulation, and the muscle\u2013brain axis with its neuroprotective myokines are also discussed. Additionally, we examine the neuro-immune axis, which mediates inflammatory responses and exacerbates neurodegeneration, and liver\u2013brain axis that is implicated in regulating neuroinflammation and promoting disease progression. Dysregulation of inter-organ pathways contributes to the systemic manifestations of neurodegenerative diseases, offering insights into both potential biomarkers and therapeutic targets, and, in turn, promising strategies for preventing, diagnosing, and treating neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/life15101499","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:19:45Z","timestamp":1758701985000},"page":"1499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inter-Organ Crosstalk in Neurodegenerative Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3801-5457","authenticated-orcid":false,"given":"Elisabetta","family":"Carata","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moris","family":"Destino","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardetta Anna","family":"Tenuzzo","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-4272","authenticated-orcid":false,"given":"Elisa","family":"Panzarini","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","first-page":"563481","article-title":"Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions","volume":"2013","author":"Sheikh","year":"2013","journal-title":"J. Neurodegener. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.tins.2019.02.007","article-title":"Neuroimmune Crosstalk through Extracellular Vesicles in Health and Disease","volume":"42","author":"Delpech","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"D\u2019Amico, G., Carista, A., Manna, O.M., Paladino, L., Picone, D., Sarullo, S., Sausa, M., Cappello, F., Vitale, A.M., and Caruso Bavisotto, C. (2024). Brain\u2013Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs. Biology, 13.","DOI":"10.3390\/biology13121056"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Savulescu-Fiedler, I., Benea, S.-N., C\u0103runtu, C., Nancoff, A.-S., Homentcovschi, C., and Bucurica, S. (2025). Rewiring the Brain Through the Gut: Insights into Microbiota\u2013Nervous System Interactions. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47070489"},{"key":"ref_5","first-page":"203","article-title":"The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems","volume":"28","author":"Carabotti","year":"2015","journal-title":"Ann. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Breit, S., Kupferberg, A., Rogler, G., and Hasler, G. (2018). Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front. Psychiatry, 9.","DOI":"10.3389\/fpsyt.2018.00044"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.gtc.2018.07.002","article-title":"Brain-Gut Axis: Clinical Implications","volume":"47","author":"Khlevner","year":"2018","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_8","first-page":"101982","article-title":"The gut microbiota-immune-brain axis: Therapeutic implications","volume":"18","author":"Moloney","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Bonfili, L., Wei, T., and Eleuteri, A.M. (2023). Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders. Nutrients, 15.","DOI":"10.3390\/nu15214631"},{"key":"ref_10","first-page":"137","article-title":"Brain-gut axis and its role in the control of food intake","volume":"55","author":"Konturek","year":"2004","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Petrut, S.M., Bragaru, A.M., Munteanu, A.E., Moldovan, A.D., Moldovan, C.A., and Rusu, E. (2025). Gut over Mind: Exploring the Powerful Gut-Brain Axis. Nutrients, 17.","DOI":"10.3390\/nu17050842"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.1007\/s00018-021-03812-y","article-title":"The enteric nervous system in gastrointestinal disease etiology","volume":"78","author":"Holland","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbi.2024.11.023","article-title":"The vagus nerve: An old but new player in brain-body communication","volume":"124","author":"Ma","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.2147\/JIR.S384949","article-title":"Vagus Nerve and Underlying Impact on the Gut Microbiota-Brain Axis in Behavior and Neurodegenerative Diseases","volume":"15","author":"Han","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.regpep.2005.07.005","article-title":"Stimulatory effect of endogenous orexin A on gastric emptying and acid secretion independent of gastrin","volume":"132","author":"Levin","year":"2005","journal-title":"Regul. Pept."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tunisi, L., Forte, N., Fern\u00e1ndez-Rilo, A.C., Mavaro, I., Capasso, R., D\u2019Angelo, L., Mili\u0107, N., Cristino, L., Di Marzo, V., and Palomba, L. (2019). Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00219"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/edrv.23.1.0454","article-title":"Orexins in the brain-gut axis","volume":"23","author":"Kirchgessner","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev-med-042320-014032","article-title":"The Gut-Brain Axis","volume":"73","author":"Mayer","year":"2022","journal-title":"Annu. Rev. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7493","DOI":"10.3390\/ijms16047493","article-title":"Impacts of Gut Bacteria on Human Health and Diseases","volume":"16","author":"Zhang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.zool.2011.04.001","article-title":"Metaorganisms as the New Frontier","volume":"114","author":"Bosch","year":"2011","journal-title":"Zoology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Intili, G., Paladino, L., Rappa, F., Alberti, G., Plicato, A., Calabr\u00f2, F., Fucarino, A., Cappello, F., Bucchieri, F., and Tomasello, G. (2023). From Dysbiosis to Neurodegenerative Diseases through Different Communication Pathways: An Overview. Biology, 12.","DOI":"10.3390\/biology12020195"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3390\/anatomia1020019","article-title":"The Microbiota Is Not an Organ: Introducing the Muco-Microbiotic Layer as a Novel Morphofunctional Structure","volume":"1","author":"Fucarino","year":"2022","journal-title":"Anatomia"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Carranza-Naval, M.J., Del Marco, A., Hierro-Bujalance, C., Alves-Martinez, P., Infante-Garcia, C., Vargas-Soria, M., Herrera, M., Barba-Cordoba, B., Atienza-Navarro, I., and Lubian-Lopez, S. (2021). Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer\u2019s Disease and Type 2 Diabetes. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2021.741923"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kaiyrlykyzy, A., Kozhakhmetov, S., Babenko, D., Zholdasbekova, G., Alzhanova, D., Olzhayev, F., Baibulatova, A., Kushugulova, A.R., and Askarova, S. (2022). Study of gut microbiota alterations in Alzheimer\u2019s dementia patients from Kazakhstan. Sci. Rep., 6.","DOI":"10.1038\/s41598-022-19393-0"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3233\/JAD-220176","article-title":"Alteration of Gut Microbiota in Alzheimer\u2019s Disease and Their Relation to the Cognitive Impairment","volume":"88","author":"Khedr","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_26","first-page":"9484217","article-title":"Kynurenine Pathway Metabolites as Biomarkers in Alzheimer\u2019s Disease","volume":"19","author":"Liang","year":"2022","journal-title":"Dis. Markers"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000526947","article-title":"Association between Gut Microbiota with Mild Cognitive Impairment and Alzheimer\u2019s Disease in a Thai Population","volume":"22","author":"Wanapaisan","year":"2022","journal-title":"Neurodegener. Dis."},{"key":"ref_28","first-page":"e0000422","article-title":"Stratification of the Gut Microbiota Composition Landscape across the Alzheimer\u2019s Disease Continuum in a Turkish Cohort","volume":"2022 22","author":"Bayraktar","year":"2022","journal-title":"mSystems"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5056\/jnm18087","article-title":"Brain-Gut-Microbiota Axis in Alzheimer\u2019s Disease","volume":"25","author":"Kowalski","year":"2019","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Braak, H., and Del Tredici, K. (2016). Potential Pathways of Abnormal Tau and \u03b1-Synuclein Dissemination in Sporadic Alzheimer\u2019s and Parkinson\u2019s Diseases. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a023630"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00401-014-1343-6","article-title":"Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats","volume":"128","author":"Holmqvist","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cell.2017.05.034","article-title":"Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways","volume":"170","author":"Bellono","year":"2017","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"G998","DOI":"10.1152\/ajpgi.00090.2004","article-title":"Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis","volume":"287","author":"Ho","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.bbi.2004.09.002","article-title":"Activation in vagal afferents and central autonomic pathways: Early responses to intestinal infection with Campylobacter jejuni","volume":"19","author":"Goehler","year":"2005","journal-title":"Brain Behav. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2307971","DOI":"10.1002\/advs.202307971","article-title":"The Brain-Gut-Bone Axis in Neurodegenerative Diseases: Insights, Challenges, and Future Prospects","volume":"11","author":"Li","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4103\/tcmj.tcmj_54_17","article-title":"Alzheimer\u2019s disease and osteoporosis","volume":"29","author":"Chen","year":"2017","journal-title":"Tzu Chi Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zemanova, N., Omelka, R., Mondockova, V., Kovacova, V., and Martiniakova, M. (2022). Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases. Biology, 11.","DOI":"10.3390\/biology11101402"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/17446651.2020.1756772","article-title":"Parkinson\u2019s disease and osteoporosis: Basic and clinical implications","volume":"15","author":"Figueroa","year":"2020","journal-title":"Expert. Rev. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41413-023-00264-x","article-title":"Modulation of bone remodeling by the gut microbiota: A new therapy for osteoporosis","volume":"11","author":"Lyu","year":"2023","journal-title":"Bone Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Morini, E., Portaro, S., Leonetti, D., De Cola, M.C., De Luca, R., Bonanno, M., Quartarone, A., and Calabr\u00f2, R.S. (2023). Bone Health Status in Individuals with Amyotrophic Lateral Sclerosis: A Cross-Sectional Study on the Role of the Trabecular Bone Score and Its Implications in Neurorehabilitation. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20042923"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhao, R. (2022). Irisin at the crossroads of inter-organ communications: Challenge and implications. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.989135"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1007\/s00415-018-9093-3","article-title":"Serum irisin is upregulated in patients affected by amyotrophic lateral sclerosis and correlates with functional and metabolic status","volume":"265","author":"Lunetta","year":"2018","journal-title":"J. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Araki, T. (2021). Gastrointestinal Status and Microbiota Shaping in Amyotrophic Lateral Sclerosis: A New Frontier for Targeting?. Amyotrophic Lateral Sclerosis [Internet], Exon Publications. Chapter 8.","DOI":"10.36255\/exonpublications.amyotrophiclateralsclerosis.2021"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"74","DOI":"10.14336\/AD.2023.0524","article-title":"Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions","volume":"15","author":"Chen","year":"2024","journal-title":"Aging Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s41392-023-01673-4","article-title":"Gut liver brain axis in diseases: The implications for therapeutic interventions","volume":"8","author":"Yan","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.coemr.2021.03.003","article-title":"Emulating the gut-liver axis: Dissecting the microbiome\u2019s effect on drug metabolism using multiorgan-on-chip models","volume":"18","author":"Lucchetti","year":"2021","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"tkaf011","DOI":"10.1093\/burnst\/tkaf011","article-title":"The role of brain-liver-gut Axis in neurological disorders","volume":"13","author":"Pan","year":"2025","journal-title":"Burns Trauma"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6733477","DOI":"10.1155\/mi\/6733477","article-title":"Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches","volume":"2025","author":"Aghara","year":"2025","journal-title":"Mediat. Inflamm."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yang, X., Qiu, K., Jiang, Y., Huang, Y., Zhang, Y., and Liao, Y. (2024). Metabolic Crosstalk between Liver and Brain: From Diseases to Mechanisms. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147621"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13024-025-00849-6","article-title":"Bridging systemic metabolic dysfunction and Alzheimer\u2019s disease: The liver interface","volume":"20","author":"Song","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11883-012-0307-3","article-title":"Dyslipidemia and the risk of Alzheimer\u2019s disease","volume":"15","author":"Reitz","year":"2013","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jackson, A., Forsyth, C.B., Shaikh, M., Voigt, R.M., Engen, P.A., Ramirez, V., and Keshavarzian, A. (2019). Diet in Parkinson\u2019s Disease: Critical Role for the Microbiome. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.01245"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/s41531-024-00816-w","article-title":"\u03b1-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice","volume":"10","author":"Morais","year":"2024","journal-title":"NPJ Park. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez Rojo, N., Blanco Ben\u00edtez, M., Cava, R., Fuentes, J.M., Canales Cort\u00e9s, S., and Gonz\u00e1lez Polo, R.A. (2024). Convergence of Neuroinflammation, Microbiota, and Parkinson\u2019s Disease: Therapeutic Insights and Prospects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111629"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113159","DOI":"10.1016\/j.expneurol.2019.113159","article-title":"Alterations of the gut microbiota with antibiotics protect dopamine neuron loss and improve motor deficits in a pharmacological rodent model of Parkinson\u2019s disease","volume":"325","author":"Koutzoumis","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/ana.27115","article-title":"Fighting amyotrophic lateral sclerosis by protecting the liver? A prospective cohort study","volume":"97","author":"Zhu","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41575-020-00385-2","article-title":"Disorders of the enteric nervous system\u2014A holistic view","volume":"18","author":"Niesler","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kurlawala, Z., McMillan, J.D., Singhal, R.A., Morehouse, J., Burke, D.A., Sears, S.M., Duregon, E., Beverly, L.J., Siskind, L.J., and Friedland, R.P. (2023). Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-32594-5"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1007\/s11481-020-09926-7","article-title":"Neuroinflammatory responses and parkinson\u2019 disease: Pathogenic mechanisms and therapeutic targets","volume":"15","author":"Yang","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.coph.2009.04.008","article-title":"Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity","volume":"9","author":"Sanjabi","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/imcb.12843","article-title":"Chemokines in neurodegenerative diseases","volume":"103","author":"Vida","year":"2025","journal-title":"Immunol. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Liu, T., Wu, H., and Wei, J. (2025). Bridging the Gap: The Neuro-immune Axis as a Key Player in Neurodegenerative Disorders. Neurosci. Bull.","DOI":"10.1007\/s12264-025-01439-8"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2014.07.012","article-title":"Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases","volume":"274","author":"Elgueta","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1523\/JNEUROSCI.1523-19.2019","article-title":"Convergence between microglia and peripheral macrophages phenotype during development and neuroinflammation","volume":"40","author":"Grassivaro","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41392-023-01628-9","article-title":"Astrocytes in human central nervous system diseases: A frontier for new therapies","volume":"8","author":"Verkhratsky","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.4103\/1673-5374.354517","article-title":"Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor regulate the interaction between astrocytes and Schwann cells at the trigeminal root entry zone","volume":"18","author":"Adam","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8189","DOI":"10.1007\/s00210-024-03188-3","article-title":"Oxidative stress-mediated neuroinflammation in Alzheimer\u2019s disease","volume":"397","author":"Firdous","year":"2024","journal-title":"Naunyn Schmiedeberg Arch. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"117253","DOI":"10.1016\/j.jns.2020.117253","article-title":"Role of mitochondrial dysfunction, oxidative stress and autophagy in progression of Alzheimer\u2019s disease","volume":"421","author":"Bhatia","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.pneurobio.2004.10.001","article-title":"Protein quality control in Alzheimer\u2019s disease by the ubiquitin proteasome system","volume":"74","author":"Fischer","year":"2004","journal-title":"Prog. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41582-024-01043-w","article-title":"\u03b1-Synuclein pathology as a target in neurodegenerative diseases","volume":"21","author":"Park","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Li, Y., Li, S., and Wu, H. (2022). Ubiquitination-proteasome system (UPS) and autophagy two main protein degradation machineries in response to cell stress. Cells, 11.","DOI":"10.3390\/cells11050851"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/s41580-024-00757-5","article-title":"Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases","volume":"25","author":"Nixon","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Xiromerisiou, G., Marogianni, C., Lampropoulos, I.C., Dardiotis, E., Speletas, M., Ntavaroukas, P., Androutsopoulou, A., Kalala, F., Grigoriadis, N., and Papoutsopoulou, S. (2022). Peripheral inflammatory markers TNF-\u03b1 and CCL2 revisited: Association with Parkinson\u2019s disease severity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010264"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Carata, E., Muci, M., Di Giulio, S., Mariano, S., and Panzarini, E. (2023). Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411251"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/cns.13569","article-title":"Peripheral inflammation and blood-brain barrier disruption: Effects and mechanisms","volume":"27","author":"Huang","year":"2021","journal-title":"CNS Neurosci. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5999","DOI":"10.3390\/cimb46060358","article-title":"The Neuromuscular Disorder Mediated by Extracellular Vesicles in Amyotrophic Lateral Sclerosis","volume":"46","author":"Carata","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Carata, E., Muci, M., Mariano, S., and Panzarini, E. (2024). BV2 Microglial Cell Activation\/Polarization Is Influenced by Extracellular Vesicles Released from Mutated SOD1 NSC-34 Motoneuron-like Cells. Biomedicines, 12.","DOI":"10.3390\/biomedicines12092069"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.mito.2021.02.008","article-title":"Mitochondrial dysfunction and traffic Jams in amyotrophic lateral sclerosis","volume":"58","author":"Jhanji","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1093\/brain\/awac091","article-title":"Motor neuron TDP-43 proteinopathy in progressive supranuclear palsy and corticobasal degeneration","volume":"145","author":"Riku","year":"2022","journal-title":"Brain"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1523\/JNEUROSCI.23-07-02627.2003","article-title":"Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons","volume":"23","author":"Rao","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Huang, X., Wang, Y.J., and Xiang, Y. (2022). Bidirectional communication between brain and visceral white adipose tissue: Its potential impact on Alzheimer\u2019s disease. EBioMedicine, 84.","DOI":"10.1016\/j.ebiom.2022.104263"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s11064-022-03569-1","article-title":"The Potential Crosstalk Between the Brain and Visceral Adipose Tissue in Alzheimer\u2019s Development","volume":"47","author":"Nguyen","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.4103\/1673-5374.369112","article-title":"Role of the adipocyte immune brain axis in Parkinson\u2019s disease: Friend or foe?","volume":"18","author":"Regensburger","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1172\/JCI126078","article-title":"Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells","volume":"130","author":"Guo","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1017\/S0007114521003962","article-title":"Adipokines: Inflammation and the pleiotropic role of white adipose tissue","volume":"127","author":"Trayhurn","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nri1937","article-title":"Adipocytokines: Mediators linking adipose tissue, inflammation and immunity","volume":"6","author":"Tilg","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1038\/s41467-020-15686-y","article-title":"Brain insulin sensitivity is linked to adiposity and body fat distribution","volume":"11","author":"Kullmann","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2337\/dc14-2319","article-title":"Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults","volume":"38","author":"Kullmann","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/jnr.23182","article-title":"Human adipose tissue-derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice","volume":"91","author":"Park","year":"2013","journal-title":"J. Neurosci. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Chen, B., and Schneeberger, M. (2024). Neuro-Adipokine Crosstalk in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115932"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.14336\/AD.2021.0422","article-title":"Potential Crosstalk Between Parkinson\u2019s Disease and Energy Metabolism","volume":"12","author":"Liu","year":"2021","journal-title":"Aging Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainres.2011.09.006","article-title":"Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson\u2019s disease","volume":"1420","author":"Zheng","year":"2011","journal-title":"Brain Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7096","DOI":"10.1007\/s12035-016-0193-8","article-title":"Relationship Between Obesity, Alzheimer\u2019s Disease, and Parkinson\u2019s Disease: An Astrocentric View","volume":"54","author":"Echeverria","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Cuvelier, E., M\u00e9quinion, M., Leghay, C., Sibran, W., Stievenard, A., Sarchione, A., Bonte, M., Vanbesien-Mailliot, C., Viltart, O., and Saitoski, K. (2018). Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00321"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1159\/000335045","article-title":"The role of ghrelin, neuropeptide Y and leptin peptides in weight gain after deep brain stimulation for Parkinson\u2019s disease","volume":"90","author":"Markaki","year":"2012","journal-title":"Stereotact. Funct. Neurosurg."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mejzini, R., Flynn, L.L., Pitout, I.L., Fletcher, S., Wilton, S.D., and Akkari, P.A. (2019). ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01310"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jns.2008.12.027","article-title":"Do Patients with Amyotrophic Lateral Sclerosis (ALS) Have Increased Energy Needs?","volume":"279","author":"Vaisman","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Lindauer, E., Dupuis, L., M\u00fcller, H.-P., Neumann, H., Ludolph, A.C., and Kassubek, J. (2013). Adipose Tissue Distribution Predicts Survival in Amyotrophic Lateral Sclerosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067783"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Chaves-Filho, A.B., Pinto, I.F.D., Dantas, L.S., Xavier, A.M., Inague, A., Faria, R.L., Medeiros, M.H.G., Glezer, I., Yoshinaga, M.Y., and Miyamoto, S. (2019). Alterations in Lipid Metabolism of Spinal Cord Linked to Amyotrophic Lateral Sclerosis. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-48059-7"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Duranti, E., and Villa, C. (2024). From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders. Biology, 13.","DOI":"10.3390\/biology13090719"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1210\/endrev\/bnaa016","article-title":"Muscle-Organ Crosstalk: The Emerging Roles of Myokines","volume":"41","author":"Severinsen","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41574-019-0174-x","article-title":"Physical activity and muscle-brain crosstalk","volume":"15","author":"Pedersen","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.freeradbiomed.2024.07.026","article-title":"Molecular aspects of the exercise response and training adaptation in skeletal muscle","volume":"223","author":"Furrer","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Liu, T., Wu, H., and Wei, J. (2025). Beyond the Brain: Exploring the multi-organ axes in Parkinson\u2019s disease pathogenesis. J. Adv. Res., 16.","DOI":"10.1016\/j.jare.2025.05.034"},{"key":"ref_107","first-page":"e70056","article-title":"Exercise intensity matters: A review on evaluating the effects of aerobic exercise intensity on muscle-derived neuroprotective myokines","volume":"11","author":"Zare","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Toader, C., Serban, M., Munteanu, O., Covache-Busuioc, R.A., Enyedi, M., Ciurea, A.V., and Tataru, C.P. (2025). From Synaptic Plasticity to Neurodegeneration: BDNF as a Transformative Target in Medicine. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094271"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Minuti, A., Raffaele, I., Scuruchi, M., Lui, M., Muscar\u00e0, C., and Calabr\u00f2, M. (2025). Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases. Antioxidants, 14.","DOI":"10.3390\/antiox14050554"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Chen, S., Chen, S.T., Sun, Y., Xu, Z., Wang, Y., Yao, S.Y., Yao, W.B., and Gao, X.D. (2019). Fibroblast growth factor 21 ameliorates neurodegeneration in rat and cellular models of Alzheimer\u2019s disease. Redox Biol., 22.","DOI":"10.1016\/j.redox.2019.101133"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbi.2010.09.006","article-title":"Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway","volume":"25","author":"Wu","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13024-024-00779-9","article-title":"The Parkinson\u2019s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons","volume":"19","author":"He","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Duranti, E., and Villa, C. (2023). Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics. Biomolecules, 13.","DOI":"10.3390\/biom13111582"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Lu, Z., Wang, Z., Zhang, X.A., and Ning, K. (2024). Myokines May Be the Answer to the Beneficial Immunomodulation of Tailored Exercise-A Narrative Review. Biomolecules, 14.","DOI":"10.3390\/biom14101205"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/10\/1499\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:35Z","timestamp":1760035715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/10\/1499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":114,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["life15101499"],"URL":"https:\/\/doi.org\/10.3390\/life15101499","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}