Beyond the Brain: The Peripheral Revolution in Neurodegenerative Diseases
DOI:
https://doi.org/10.59736/IJP.24.02.1100Keywords:
Neutodegenerative diseases, Gut-brain axis, neuroinflammation, immune systemAbstract
Neurodegenerative disorders were considered diseases limited to the brain. However, the growing evidence clearly indicates that these are the diseases affecting the whole body due to the complex interplay of the brain with the peripheral organs. Recently published data stress the role of the gut microbiota, liver, kidneys, immune system, and vasculature in controlling neuroinflammation, protein misfolding, and neurodegeneration. This is a significant shift from the brain-focused approach and can explain why most of the neuroprotective strategies developed so far failed to show their clinical effectiveness. This editorial aims to present the discussion on how the systems biology perspective should be applied to better understand the disease pathogenesis and translational implications. Multi-omics, artificial intelligence, and precision medicine will open the way to the development of biomarkers and therapies personalized for every patient.
References
Jahan S, Ikram M, Siraj S, Ullah S, Zakria M, Ahmad N. Emodin, a potent anthraquinone mitigates MPTP-induced Parkinsons' disease pathology by regulating Nrf2 and its downstream targets: in silico and in vivo approach. Mol Neurobiol. 2025;62(7):8103-8120. https://doi.org/10.1007/s12035-025-04762-3.
Mahnoor, Jahan S, Elahi L, Zakria M, Rabia, Ikram M, Ullah N. Alpha-linolenic acid for mitigating neuroinflammation and dopaminergic neuronal loss in Parkinson's disease: insights from in vivo and in silico studies. Clin Exp Pharmacol Physiol. 2025;52(6):e70043. https://doi.org/10.1111/1440-1681.70043
Panghal A, Flora SJ. Nano-based approaches for the treatment of neuro-immunological disorders: A special emphasis on multiple sclerosis. Discover Nano. 2024;19(1):171. https://doi.org/10.1186/s11671-024-04121-6
Sheikh AM, Yano S, Tabassum S, Nagai A. The role of the vascular system in degenerative diseases: mechanisms and implications. Int J Mol Sci. 2024;25(4):2169. https://doi.org/10.3390/ijms25042169
Fymat AL. The diseased brain: neurodegenerative and other diseases. J Neurol Psychol Res. 2024;5(1):1-54.
Matsubara Y, Kiyohara H, Teratani T, Mikami Y, Kanai T. Organ and brain crosstalk: the liver-brain axis in gastrointestinal, liver, and pancreatic diseases. Neuropharmacology. 2022;205:108915. https://doi.org/10.1016/j.neuropharm.2021.108915
Chakrabarti A, Geurts L, Hoyles L, Iozzo P, Kraneveld AD, La Fata G, et al. The microbiota-gut-brain axis: pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice. Cell Mol Life Sci. 2022;79(2):80. https://doi.org/10.1007/s00018-022-04173-2
Padhi P, Worth C, Zenitsky G, Jin H, Sambamurti K, Anantharam V, et al. Mechanistic insights into gut microbiome dysbiosis-mediated neuroimmune dysregulation and protein misfolding and clearance in the pathogenesis of chronic neurodegenerative disorders. Front Neurosci. 2022;16:836605. https://doi.org/10.3389/fnins.2022.836605
Yang R, Gao G, Yang H. The pathological mechanism between the intestine and brain in the early stage of Parkinson's disease. Front Aging Neurosci. 2022;14:861035. https://doi.org/10.3389/fnagi.2022.861035
Kaur R, Kumar S, Singh L. A comprehensive review: neuroinflammation and immune communication between the central nervous system and the periphery. Cytokine. 2025;192:156974. https://doi.org/10.1016/j.cyto.2025.156974
Strzelec M, Detka J, Mieszczak P, Sobocińska MK, Majka M. Immunomodulation—a general review of the current state-of-the-art and new therapeutic strategies for targeting the immune system. Front Immunol. 2023;14:1127704. https://doi.org/10.3389/fimmu.2023.1127704
Jahan S, Khan M, Mukhtar H, Khan SA, Rehman IU, Qazi N. Immuno-modulating properties of Aloe vera and its efficacy in immune mediated disorders. International Journal of Pathology. 2021:200-6.
Ali H. Artificial intelligence in multi-omics data integration: Advancing precision medicine, biomarker discovery and genomic-driven disease interventions. Int J Sci Res Arch. 2023;8(1):1012-1030. https://doi.org/10.30574/ijsra.2023.8.1.0129
Published
Issue
Section
License
Copyright (c) 2026 Sarwat Jahan, Muhammad Ikram, Zeeshan Khan
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Readers may “Share-copy and redistribute the material in any medium or format” and “Adapt-remix, transform, and build upon the material”. The readers must give appropriate credit to the source of the material and indicate if changes were made to the material. Readers may not use the material for commercial purpose. The readers may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
