Neuroinflammation as a central link in the pathogenesis of neurodegenerative diseases: molecular mechanisms, clinical correlates, and therapeutic perspectives
https://doi.org/10.33667/2782-4101-2025-3-7-12
Abstract
Neuroinflammation is regarded as a central mechanism driving the progression of neurodegenerative diseases, integrating age-associated inflammation, glial dysfunction, blood–brain barrier disruption, mitochondrial stress, and systemic factors. Activation of microglia and astrocytes, involvement of the NLRP3 inflammasome, dysregulation of TREM2 signaling, disturbances in iron and lipid metabolism, as well as the influence of the microbiota and metabolic comorbidities together form a self-sustaining pathological network that exacerbates neuronal loss in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Emerging therapeutic strategies include modulation of microglia, inhibition of inflammasome-related cascades, epigenetic approaches, and nanotechnology-based delivery systems for anti-inflammatory compounds; however, their clinical efficacy remains limited. A deeper understanding of the architecture of neuroinflammation opens avenues for the development of targeted and personalized interventions.
About the Authors
S. M. Gasanova
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation
Russian Federation
Gasanova Sakinat Mirzaevna
Moscow
A. D. Sandzhigoryaeva
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation
Russian Federation
Sandzhigoryaeva Alexandra Dordzhievna
Moscow
S. A. Mikailova
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation
Russian Federation
Mikailova Samira Aminullaevna
Moscow
A. V. Uyutnova
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation
Russian Federation
Uyutnova Anna Vladimirovna
Moscow
R. F. Safina
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation
Russian Federation
Safina Renata Faritovna
Moscow
References
1. Nichols E, Steinmetz JD, Vollset SE, et al. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7(2):e105–e125. https://doi.org/10.1016/S2468-2667(21)00249-8.
2. GBD 2021 Nervous System Disorders Collaborators. Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024;23(4):344–381. https://doi.org/10.1016/S1474-4422(24)00038-3.
3. Dorsey ER, Elbaz A, Nichols E, et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):939–953. https://doi.org/10.1016/S1474-4422(18)30295-3.
4. Balistreri CR, Monastero R. Neuroinflammation and neurodegenerative diseases: how much do we still not know? Brain Sci. 2024;14(1):19. https://doi.org/10.3390/brainsci14010019.
5. Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14(7):463–477. https://doi.org/10.1038/nri3705.
6. Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405. https://doi.org/10.1016/S1474-4422(15)70016-5.
7. Shi FD, Yong VW. Neuroinflammation across neurological diseases. Science. 2025;388(6753):eadx0043. https://doi.org/10.1126/science.adx0043.
8. Wheeler MA, Quintana FJ. The neuroimmune connectome in health and disease. Nature. 2025;638(8043):333–342. https://doi.org/10.1038/s41586-024-08474-x.
9. Xu Y, Jin MZ, Yang ZY, et al. Microglia in neurodegenerative diseases. Neural Regen Res. 2021;16(2):270–280. https://doi.org/10.4103/1673-5374.290881.
10. Wendimu MY, Hooks SB. Microglia phenotypes in aging and neurodegenerative diseases. Cells. 2022;11(13):2091. https://doi.org/10.3390/cells11132091.
11. Anderson FL, Biggs KE, Rankin BE, et al. NLRP3 inflammasome in neurodegenerative disease. Transl Res. 2023;252:21–33. https://doi.org/10.1016/j.trsl.2022.08.006.
12. Linnerbauer M, Wheeler MA, Quintana FJ. Astrocyte crosstalk in CNS inflammation. Neuron. 2020;108(4):608–622. https://doi.org/10.1016/j.neuron.2020.08.012.
13. Zhao Y, Wang L, Wang J, et al. Astrocyte-mediated neuroinflammation in neurological disorders. Biomolecules. 2024;14(10):1204. https://doi.org/10.3390/biom14101204.
14. Yang J, Ran M, Li H, et al. New insight into neurological degeneration: inflammatory cytokines and blood–brain barrier. Front Mol Neurosci. 2022;15:1013933. https://doi.org/10.3389/fnmol.2022.1013933.
15. Mayer MG, Fischer T. Microglia at the blood–brain barrier in health and disease. Front Cell Neurosci. 2024;18:1360195. https://doi.org/10.3389/fncel.2024.1360195.
16. Ma Y, Zhou X, Guo Y, et al. Epigenetic regulation of neuroinflammation in Alzheimer’s disease. Cells. 2024;13(1):79. https://doi.org/10.3390/cells13010079.
17. Lewis BA, Hanover JA. O-GlcNAc and the epigenetic regulation of gene expression. J Biol Chem. 2014;289(50):34440–34448. https://doi.org/10.1074/jbc.R114.595439
18. Yan H, Wang W, Cui T, et al. Advances in the understanding of the correlation between neuroinflammation and microglia in Alzheimer’s disease. Immunotargets Ther. 2024;13:287–304. https://doi.org/10.2147/ITT.S455881.
19. Hanslik KL, Ulland TK. The role of microglia and the NLRP3 inflammasome in Alzheimer’s disease. Front Neurol. 2020;11:570711. https://doi.org/10.3389/fneur.2020.570711.
20. Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol. 2007;208(1):1–25. https://doi.org/10.1016/j.expneurol.2007.07.004.
21. Zeng W, Cai J, Zhang L, et al. Iron deposition in Parkinson’s disease: a mini-review. Cell Mol Neurobiol. 2024;44:26. https://doi.org/10.1007/s10571-024-01459-4.
22. You J, Youssef MMM, Santos JR, et al. Microglia and astrocytes in amyotrophic lateral sclerosis: disease-associated states, pathological roles, and therapeutic potential. Biology (Basel). 2023;12(10):1307. https://doi.org/10.3390/biology12101307.
23. Doroszkiewicz J, Winkel I, Mroczko B. Comparative analysis of neuroinflammatory pathways in Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis: insights into similarities and distinctions. Front Neurosci. 2025;19:1579511. https://doi.org/10.3389/fnins.2025.1579511.
24. Lassmann H. Mechanisms of neurodegeneration shared between multiple sclerosis and Alzheimer’s disease. J Neural Transm. 2011;118(5):747–752. https://doi.org/10.1007/s00702-011-0607-8.
25. Loh JS, Mak WQ, Tan LKS, et al. Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther. 2024;9(1):37. https://doi.org/10.1038/s41392-024-01743-1.
26. Kacířová M, Zmeškalová A, Kořínková L, et al. Inflammation: major denominator of obesity, type 2 diabetes and Alzheimer’s disease-like pathology? Clin Sci (Lond). 2020;134(5):547–570. https://doi.org/10.1042/CS20191313.
27. Toledano A, Rodríguez-Casado A, Álvarez MI, et al. Alzheimer’s disease, obesity, and type 2 diabetes: focus on common neuroglial dysfunctions. Brain Sci. 2024;14(11):1101. https://doi.org/10.3390/brainsci14111101.
28. Xie J, Van Hoecke L, Vandenbroucke RE. The impact of systemic inflammation on Alzheimer’s disease pathology. Front Immunol. 2022;12:796867. https://doi.org/10.3389/fimmu.2021.796867.
29. Noh MY, Kwon HS, Kwon MS, et al. Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions. Mol Neurodegener. 2025;20(1):82. https://doi.org/10.1186/s13024-025-00867-4.
30. Koga-Batko J, Antosz-Popiołek K, Nowakowska H, et al. Nanoparticles as an encouraging therapeutic approach to Alzheimer’s disease. Int J Mol Sci. 2025;26(16):7725. https://doi.org/10.3390/ijms26167725.
Review
For citations:
Gasanova S.M., Sandzhigoryaeva A.D., Mikailova S.A., Uyutnova A.V., Safina R.F. Neuroinflammation as a central link in the pathogenesis of neurodegenerative diseases: molecular mechanisms, clinical correlates, and therapeutic perspectives. International journal of Innovative Medicine. 2025;(3):7-12. https://doi.org/10.33667/2782-4101-2025-3-7-12
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