Inflammation in the pathogenesis of neurodegenerative diseases
- Autores: Goncharov A.G.1, Reverchuk I.V.1, Shupletsova V.V.1
-
Afiliações:
- Immanuel Kant Baltic Federal University
- Edição: Volume 20, Nº 2 (2023)
- Páginas: 5-11
- Seção: Научные обзоры
- URL: https://cijournal.ru/1684-7849/article/view/627304
- DOI: https://doi.org/10.17816/CI627304
- ID: 627304
Citar
Texto integral
Acesso está concedido
Acesso é pago ou somente para assinantes
Resumo
INTRODUCTION: Neurodegenerative diseases are common chronic disorders that are associated with progressive damage to the nervous system. The role of the immune system in the development of neurodegenerative diseases was confirmed by data on the activation of microglia, the presence of an imbalance in the composition and phenotype of peripheral immune cells, and the presence of humoral immunity disorders and intestinal microbiota dysbiosis in patients with this pathology.
DISCUSSION: Inflammation has been observed to play a key role in the pathogenesis of diseases associated with progressive damage to the nervous system. The article analyzes the mechanisms in the development of “subclinical” chronic inflammation that leads to development of old-age-related diseases, including neurodegenerative pathology. At least three groups of factors associated with old age play a role in the formation of a proinflammatory status: mitochondrial dysfunction, development of an age-related proinflammatory status of the immune system, and chronic stress. Mitochondrial dysfunction is primarily associated with disruption of mitophagy processes: failure of quality control mechanisms as a result of disruption of mitophagy processes leads to the accumulation of terminally damaged mitochondria, which become a threat to cell survival. Inadequate removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and the development of inflammatory diseases. A high level of deletions in the mitochondrial genetic apparatus that accumulates with age inevitably leads to increased formation of reactive oxygen species, which in turn are assumed as one of the leading activators of the cytosolic NLRP3 protein, the primary component of inflammasomes. Increased inflammasome formation eventually leads to caspase-1-dependent production of proinflammatory interleukins. Age-related inflammatory imbalance is associated with the fact that the immune system, the main protective mechanism characterized by the inflammatory response, copes with constant antigenic attacks. However, over time, upon reaching a certain threshold, the reaction of the immune system becomes excessive, characterized by increased production of coagulation factors, proinflammatory cytokines, acute phase proteins of inflammation, prostaglandins, and leukotrienes.
CONCLUSIONS: Immunological changes that develop during chronic (long-term) stress are the result of a disruption of the homeostatic connection between the neuroendocrine and immune systems, leading to the formation of an inflammatory background that complements the “proinflammatory status” that develops as a result of age-related changes in the immune system and disruption of mitophagy mechanisms.
Palavras-chave
Texto integral
Sobre autores
Andrey Goncharov
Immanuel Kant Baltic Federal University
Email: agoncharov59@mail.ru
ORCID ID: 0000-0001-6967-8838
Código SPIN: 6638-9367
MD, Cand. Sci. (Medicine)
Rússia, KaliningradIgor Reverchuk
Immanuel Kant Baltic Federal University
Email: igor7272igor@gmail.com
ORCID ID: 0000-0002-3498-9094
Código SPIN: 1506-1036
MD, Dr. Sci. (Medicine)
Rússia, KaliningradValeria Shupletsova
Immanuel Kant Baltic Federal University
Autor responsável pela correspondência
Email: vshupletsova@mail.ru
ORCID ID: 0000-0001-7243-9731
Código SPIN: 5736-4492
Cand. Sci. (Biology)
Rússia, KaliningradBibliografia
- Pezone A, Olivieri F, Napoli MV, et al. Inflammation and DNA damage: cause, effect or both. Nat Rev Rheumatol. 2023;19(4):200–211. doi: 10.1038/s41584-022-00905-1
- Contaldi E, Magistrelli L, Comi C. Disease mechanisms as subtypes: Immune dysfunction in Parkinson’s disease. Handb Clin Neurol. 2023;193:67–93. doi: 10.1016/B978-0-323-85555-6.00008-4
- Intili G, Paladino L, Rappa F, et al. From Dysbiosis to Neurodegenerative Diseases through Different Communication Pathways: An Overview. Biology (Basel). 2023;12(2):195. doi: 10.3390/biology12020195
- Zhang L, Wang Y, Liu T, Mao Y, Peng B. Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders. Neurosci Bull. 2023;39(3):491–502. doi: 10.1007/s12264-022-01013-6 Erratum in: Neurosci Bull. 2023;39(3):557. doi: 10.1007/s12264-023-01026-9
- Gankovskaya LV, Artem’eva OV, Namazova-Baranova LS, et al. Immunological aspects of aging and age-associated pathology. Moscow: Pediatr; 2021. 156 p. (In Russ). EDN: SYHTBM
- Zhang H, Wang Z, Wang G, et al. Understanding the Connection Between Gut Homeostasis and Psychological Stress. J Nutr. 2023;153(4):924–939. doi: 10.1016/j.tjnut.2023.01.026
- Franceschi C., Bonafè M., Valensin S., et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–254. doi: 10.1111/j.1749-6632.2000.tb06651.x
- Brookes PS. Mitochondrial H(+) leak and ROS generation: an odd couple. Free Radic Biol Med. 2005;38(1):12–23. doi: 10.1016/j.freeradbiomed.2004.10.016
- Choubey V, Zeb A, Kaasik A. Molecular Mechanisms and Regulation of Mammalian Mitophagy. Cells. 2021;11(1):38. doi: 10.3390/cells11010038
- Dabravolski SA, Nikiforov NG, Zhuravlev AD, et al. Role of the mtDNA Mutations and Mitophagy in Inflammaging. Int J Mol Sci. 2022;23(3):1323. doi: 10.3390/ijms23031323
- Prasun P. Mitochondrial dysfunction in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165838. doi: 10.1016/j.bbadis.2020.165838
- Casanova A., Wevers A., Navarro-Ledesma S., Pruimboom L. Mitochondria: It is all about energy. Front Physiol. 2023;14:1114231. doi: 10.3389/fphys.2023.1114231
- Anderson FL, Biggs KE, Rankin BE, Havrda MC. NLRP3 inflammasome in neurodegenerative disease. Transl Res. 2023;252:21–33. doi: 10.1016/j.trsl.2022.08.006
- Soraci L, Gambuzza ME, Biscetti L, et al. Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: mechanisms and therapeutic implications. J Neurol. 2023;270(3):1346–1360. doi: 10.1007/s00415-022-11491-3
- Fard MT, Savage KM, Stough CK. Peripheral inflammation marker relationships to cognition in healthy older adults — A systematic review. Psychoneuroendocrinology. 2022. Vol. 144. P. 105870. doi: 10.1016/j.psyneuen.2022.105870
- Sanchez-Roman I, Ferrando B, Holst CM, et al. Molecular markers of DNA repair and brain metabolism correlate with cognition in centenarians. Geroscience. 2022;44(1):103–125. doi: 10.1007/s11357-021-00502-2
- Kerr JS, Adriaanse BA, Greig NH, et al. Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms. Trends Neurosci. 2017;40(3):151–166. doi: 10.1016/j.tins.2017.01.002
- Swerdlow RH. Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease. J Alzheimers Dis. 2018;62(3):1403–1416. doi: 10.3233/JAD-170585
- Wang S, Deng Z, Ma Y, et al. The Role of Autophagy and Mitophagy in Bone Metabolic Disorders. Int J Biol Sci. 2020;16(14):2675–2691. doi: 10.7150/ijbs.46627
- Mary A, Eysert F, Checler F, Chami M. Mitophagy in Alzheimer’s disease: Molecular defects and therapeutic approaches. Mol Psychiatry. 2023;28(1):202–216. doi: 10.1038/s41380-022-01631-6
- Zeng K, Yu X, Mahaman YAR, et al. Defective mitophagy and the etiopathogenesis of Alzheimer’s disease. Transl Neurodegener. 2022;11(1):32. doi: 10.1186/s40035-022-00305-1
- Castillo-Rangel C, Marin G, Hernández-Contreras KA, et al. Neuroinflammation in Parkinson’s Disease: From Gene to Clinic: A Systematic Review. Int J Mol Sci. 2023;24(6):5792. doi: 10.3390/ijms24065792
- Kouli A, Torsney KM, Kuan WL. Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects [Internet]. Brisbane (AU): Codon Publications; 2018. Chapter 1. doi: 10.15586/codonpublications.parkinsonsdisease.2018.ch1
- Vignjević Petrinović S, Milošević MS, Marković D, Momčilović S. Interplay between stress and cancer-A focus on inflammation. Front Physiol. 2023;14:1119095. doi: 10.3389/fphys.2023.1119095
- Black PH. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun. 2003;17(5):350–364. doi: 10.1016/s0889-1591(03)00048-5
- Prokhorenko IO, Germanova VN, Sergeev OS. Stress and state of the immune system in norm and pathology. Brief review of literature. Vestnik meditsinskogo instituta «REAVIZ». Reabilitatsiya, Vrach i Zdorov’ye. 2017;(1(25)):82–90. (In Russ). EDN: YLFZHH
- Cohen S, Janicki-Deverts D, Doyle WJ, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A. 2012;109(16):5995–5999. doi: 10.1073/pnas.1118355109
- Hassamal S. Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories. Front Psychiatry. 2023;14:1130989. doi: 10.3389/fpsyt.2023.1130989
- Karvandi MS, Sheikhzadeh Hesari F, Aref AR, Mahdavi M. The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation. Front Cell Neurosci. 2023;17:1105247. doi: 10.3389/fncel.2023.1105247
- Bartolomucci A, Palanza P, Sacerdote P, et al. Social factors and individual vulnerability to chronic stress exposure. Neurosci Biobehav Rev. 2005;29(1):67–81. doi: 10.1016/j.neubiorev.2004.06.009
- Masafi S, Saadat SH, Tehranchi K, et al. Effect of Stress, Depression and Type D Personality on Immune System in the Incidence of Coronary Artery Disease. Open Access Maced J Med Sci. 2018;6(8):1533–1544. doi: 10.3889/oamjms.2018.217