Abstract

In neurodegenerative diseases, activation of the innate immunity system plays an important pathogenicmechanism(3). The dysfunction of the nervous system leads to neurodegenerative disorders. Parkinson’s disease (PD), motor neuron diseases (MND), multiple system atrophy (MSA), Alzheimer’sdisease (AD), and frontotemporal dementia (FTD) are amongst some most studied neurodegenerative disorders (NDDs). These disorders happen due to the progressive deterioration of neurons especiallypresent in the brain, which leads to a variety of symptoms, including cognitive failure, motorweakening, and deviations in behaviour. Recent experimental and clinical studies have shown that innate immune activation and neuroinflammation are significant hallmarks of neurodegenerativeprocesses which also contribute to the development of eurodegenerative disorders with itscharacterization. The multidisciplinary approach can be used to understand the complex relationshipbetween innate immunity and neurodegeneration. System biology and bioinformatics play a verycrucial role in understanding the connection between the nervous system and immunology, especially inthe case of neurodegenerative disorders. This interdisciplinary approach integrates computationalbiology, system biology, artificial intelligence, and machine learning to understand the disordermechanism, identifying biomarkers and potential treatment strategies for neurodegeneration. In thisreview article, we are going to overview the innate immune system and how its dysregulation plays acrucial role in neurodegenerative disorders. Also, the importance of system biology andbioinformaticsin Neuro-immunology.

• 1.   National Cancer Institute. https://www. cancer.gov/publications/dictionaries/cancerterms/def/innate-immunity [Internet]. www.
• 2.   Diamond M.S., Kanneganti T.D. Innate immunity: the First Line of Defense against SARS-CoV-2. Nature Immunology [Internet].
• 3.   Castro-Gomez S., Heneka M.T. Innate immune activation in neurodegenerative diseases. Immunity [Internet]. 2024 Apr [cited 2024 Oct
• 4.   Lamptey R., Chaulagain B., Trivedi R., Gothwal A., Layek B., Singh J. A Review of the Common Neurodegenerative Disorders:
• 5.   Kwon H.S., Koh S.H. Neuroinflammation in Neurodegenerative Disorders: the Roles of Microglia and Astrocytes. Translational
• 6.   Cai Y., Liu J, Wang B., Sun M., Yang H. Microglia in the Neuroinflammatory Pathogenesis of Alzheimer’s Disease and Related Therapeutic
• 7.   Chowdhury U.N, Ahmad S., Islam M.B., Alyami S.A., Quinn JMW, Eapen V., et al. System biology and bioinformatics pipeline
• 8.   Aborode A.T., Emmanuel O.A., Onifade I.A., Olotu E., Otorkpa O.J., Mehmood Q., et al. The role of machine learning in discovering
• 9.   Colonna M, Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annual Review of
• 10.   Bachiller S., Jiménez-Ferrer I, Paulus A., Yang Y., Swanberg M., Deierborg T., et al. Microglia
• 11.   Li D., Wu M. Pattern Recognition Receptors in Health and Diseases. Signal Transduction and Targeted Therapy. 2021 Aug 4; 6(1): 1–24.
• 12.   Adamu A., Li S., Gao F., Xue G. The role of neuroinflammation in neurodegenerative diseases: current understanding and future
• 13.   Vicidomini C., Fontanella F., Tiziana D’Alessandro, Roviello G.N. A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases. Biomolecules. 2024 Oct 19; 14(10): 1330–0.
• 14.   Gao W., Jing S., He C., Saberi H., Sharma H.S., Han F., et al. Advancements in neurodegenerative diseases: Pathogenesis and novel neurorestorative interventions. Journal of Neurorestoratology [Internet]. 2024 Dec 22; 13(2): 100176. Available from: https:// www.sciencedirect.com/science/article/pii/ S2324242624000834 ,
• 15.   Huang Y., Zhang G., Li S, Feng J., Zhang Z. Innate and adaptive immunity in neurodegenerative disease. Cellular and Molecular Life Sciences [Internet]. 2025 Feb 2 [cited 2025 Feb 9]; 82(1). Available from: https://pmc.ncbi.nlm.nih. gov/articles/PMC11788272/.
• 16.   Rather M.A., Khan A., Alshahrani S., Rashid H., Qadri M., Rashid S., et al. Inflammation and Alzheimer’s Disease: Mechanisms and Therapeutic Implications by Natural Products. Oliveira SHP, editor. Mediators of Inflammation. 2021 Aug 2; 2021: 1–21..
• 18.   Pajares M., I. Rojo A., Manda G., Boscá L., Cuadrado A. Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications. Cells. 2020 Jul 14; 9(7): 1687.
• 19.   Zierfuss B., Larochelle C., Prat A. Blood-brain barrier dysfunction in multiple sclerosis: causes, consequences, and potential effects of therapies. The Lancet Neurology. 2024 Jan 1; 23(1): 95–109.
• 20.   Provenzano F, Torazza C, Bonifacino T, Bonanno G, Milanese M. The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity. International Journal of Molecular Sciences [Internet]. 2023 Jan 1;
• 21.   Ellrichmann G., Reick C., Saft C., Linker R.A. The role of the immune system in Huntington’s disease. Clinical & Developmental Immunology [Internet]. 2013; 2013: 541259. Available from: https://pubmed.ncbi.nlm.nih. gov/23956761/
• 22.   ZhangW.,XiaoD., Mao Q., Xia H. Role of neuroinflammation in neurodegeneration development. Nature [Internet]. 2023 Jul 12; 8(1). Available from: https://www.nature. com/articles/s41392-023-01486-5.
• 23.   Dhillon B.K., Smith M., Baghela A., Lee AHY, Hancock REW. Systems Biology Approaches to Understanding the Human Immune System. Frontiers in Immunology. 2020 Jul 30;11.
• 24.   Relucocoss, Popescu B.O. Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multiomics lens. Human Genomics. 2024 Dec 31;18(1).
• 25.   Li M.M., Huang Y., Sumathipala M., Man Qing Liang, Valdeolivas A, Ananthakrishnan A.N., et al. Contextual AI models for single-cell protein biology. Nature Methods [Internet]. 2024 Jul 22 [cited 2024 Aug 17]; Available from: https:// www.nature.com/articles/s41592-024-02341-3
• 26.   Wang H., Li J., Tu W., Wang Z., Zhang Y., Chang L, et al. Identification of Blood Biomarkers Related to Energy Metabolism and Construction of Diagnostic Prediction Model Based on Three Independent Alzheimer’s Disease Cohorts. Journal of Alzheimer s Disease [Internet]. 2024 Jul 30 [cited 2025 Feb 9]; 100(4): 1261–87. Available from: https://pmc.
• 27.   Pernice S., Follia L., Maglione A., Pennisi M., Pappalardo F., Novelli F., et al. Computational modelling of the immune response in multiple sclerosis using epimod framework. BMC Bioinformatics. 2020 Dec 1;21(S17).
• 28.   Kian Talaei, Garan S.A., Barbara, Olufsen MS, Cho J., Jahansooz J.R., et al. A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus. Frontiers in Cellular and Infection
• 29.   La Cognata V., Morello G., Cavallaro S. Omics Data and Their Integrative Analysis to Support Stratified Medicine in Neurodegenerative Diseases. International Journal of Molecular Sciences. 2021 May 1; 22(9): 4820.
• 30.   Gao C., Jiang J., Tan Y., Chen S. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduction and Targeted Therapy. 2023 Sep 22; 8(1): 1–37.
• 31.   Dar M.A., Arafah A., Bhat K.A., Khan A., Khan M.S., Ali A., et al. Multiomics technologies: role in disease biomarker discoveries and therapeutics. Briefings in Functional Genomics. 2022 Jul 9.

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Funding