ALZHEİMER HASTALIĞINDA KOMPLEMAN SİSTEMİN ROLÜ
Yıl 2024,
Cilt: 48 Sayı: 1, 300 - 311, 20.01.2024
Anıl Yirün
,
Selinay Başak Erdemli Köse
,
Pınar Erkekoğlu
Öz
Amaç: Bağışıklık sistemi, vücudu enfeksiyonlara karşı savunan, yabancı maddelere tepki oluşturan ve hastalık gibi durumlarda organizmayı koruyan bir sistemdir. Merkezi sinir sistemi bağışıklık yanıtları bakımından periferik organlardan farklı benzersiz bir yapıya sahiptir. Son yıllarda gerçekleştirilen kapsamlı araştırmalar, beyin ve bağışıklık sistemi arasında karmaşık bir etkileşim olduğunu göstermiştir. Beyin bağışıklık sistemi, merkezi sinir sistemi içinde yer alan bir dizi hücresel ve moleküler mekanizmadan ve bağışıklık hücreleri ve moleküllerinin yer aldığı bir dizi yapıdan oluşan kompleks bir sistemdir. Beyindeki kronik inflamasyonun birçok nörodejeneratif hastalıkta ilerleyici nöron ölümünde önemli bir rol oynayabileceği bilinmektedir. Son yıllarda başta kadınlar olmak üzere ileri yaş popülasyonu etkileyen Alzheimer hastalığı, kısa süreli hafıza, biliş ve günlük yaşam aktivitelerinde zorluklarla ilgili sorunlarla karakterize edilen ilerleyici, nörodejeneratif bir hastalıktır. Alzheimer hastalığı genetik, immün ve çevresel etmenleri de içerdiği düşünülen kompleks bir mekanizmayla ortaya çıkar. Bu hastalığın kesin bir tedavisi yoktur ve kullanılan ilaçlar ancak semptomları geciktirir. Kompleman sistem doğuştan gelen bağışıklık sisteminin bir parçasıdır. Bu sistemin üç farklı aktive edici yolu vardır ve nihai olarak hedef hücre lizisine neden olan bir membran saldırı kompleksinin oluşumuyla sonuçlanır.
Sonuç ve Tartışma: Bu derlemede kompleman sistemin merkezi sinir sisteminde işleyişine ve Alzheimer hastalığı gibi nörodejeneratif bozukluklara yol açan kronik nöroinflamasyona nasıl katkıda bulunduğuna dair bilgiler paylaşılması amaçlanmıştır.
Kaynakça
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- 2. Veerhuis, R., Nielsen, H.M., Tenner, A.J. (2011). Complement in the brain. Molecular Immunology, 48(14), 1592-1603. [CrossRef]
- 3. Crehan, H., Hardy, J., Pocock, J. (2012). Microglia, Alzheimer's disease, and complement. International Journal of Alzheimer's disease, 2012, 983640. [CrossRef]
- 4. Ueno, M., Chiba, Y., Murakami, R., Matsumoto, K., Kawauchi, M., Fujihara, R. (2016). Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions. Brain Tumor Pathology, 33(2), 89-96. [CrossRef]
- 5. Morgan, B.P. (2018). Complement in the pathogenesis of Alzheimer's disease. Seminars in Immunopathology, 40(1), 113-124. [CrossRef]
- 6. Montagne, A., Barnes, S.R., Sweeney, M.D., Halliday, M.R., Sagare, A.P., Zhao, Z., Toga, A.W., Jacobs, R. E., Liu, C.Y., Amezcua, L., Harrington, M.G., Chui, H.C., Law, M., Zlokovic, B.V. (2015). Blood-brain barrier breakdown in the aging human hippocampus. Neuron, 85(2), 296-302. [CrossRef]
- 7. Varatharaj, A., Galea, I. (2017). The blood-brain barrier in systemic inflammation. Brain, Behavior, and Immunity, 60, 1-12. [CrossRef]
- 8. Takeda, S., Sato, N., Morishita, R. (2014). Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Frontiers in Aging Neuroscience, 6, 171. [CrossRef]
- 9. McGeer, E.G., McGeer, P.L. (1998). The importance of inflammatory mechanisms in Alzheimer disease. Experimental Gerontology, 33(5), 371-378. [CrossRef]
- 10. Shinjyo, N., Kagaya, W., Pekna, M. (2021). Interaction between the complement system and ınfectious agents-A potential mechanistic link to neurodegeneration and dementia. Frontiers in Cellular Neuroscience, 15, 710390. [CrossRef]
- 11. Mapunda, J.A., Tibar, H., Regragui, W., Engelhardt, B. (2022). How does the immune system enter the brain? Frontiers in Immunology, 13, 805657. [CrossRef]
- 12. Shah, A., Kishore, U., Shastri, A. (2021). Complement system in Alzheimer's disease. International Journal of Molecular Sciences, 22(24), 13647. [CrossRef]
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- 14. Kumar, P.J., Clark, M. (2011). Kumar & Clark’s Clinical Medicine, Saunders Elsevier, Edinburgh.
- 15. Tenner A.J. (2020). Complement-mediated events in Alzheimer’s disease: Mechanisms and potential therapeutic targets. Journal of Immunology, 204(2), 306-315. [CrossRef]
- 16. Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S.G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., Cooper, C., Fox, N., Gitlin, L.N., Howard, R., Kales, H.C., Larson, E. B., Ritchie, K., Rockwood, K., Sampson, E.L., Samus, Q., Schneider, L.S., Selbæk, G., Teri, L., Mukadam, N. (2017). Dementia prevention, intervention, and care. Lancet, 390(10113), 2673-2734. [CrossRef]
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- 18. Shastri, A., Bonifati, D.M., Kishore, U. (2013). Innate immunity and neuroinflammation. Mediators of inflammation, 2013, 342931. [CrossRef]
- 19. Liu, Y.P., Lin, H.I., Tzeng, S.F. (2005). Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. Brain Research, 1054(2), 152-158. [CrossRef]
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THE ROLE OF THE COMPLEMENT SYSTEM IN ALZHEIMER’S DISEASE
Yıl 2024,
Cilt: 48 Sayı: 1, 300 - 311, 20.01.2024
Anıl Yirün
,
Selinay Başak Erdemli Köse
,
Pınar Erkekoğlu
Öz
Objective: Immune system is a system that defends the body against infections, reacts to foreign substances, and protects the organism in conditions such as illness. The central nervous system has a unique structure that differs from peripheral organs in terms of immune responses. Extensive research in recent years has shown that there is a complex interaction between the brain and immune system. Brain immune system is a complex system consisting of a number of cellular and molecular mechanisms within the central nervous system and a set of structures in which immune cells and molecules take place. It is known that chronic inflammation in the brain may play an important role in progressive neuron death in many neurodegenerative diseases. Alzheimer's disease, which has been affecting the elderly population, especially women in recent years, is a progressive, neurodegenerative disease characterized by problems related to short-term memory, cognition and difficulties in daily living activities. Alzheimer's disease occurs with a complex mechanism thought to include genetic, immune and environmental factors. There is no definite cure for this disease and the drugs used only delay the symptoms. The complement system is part of the innate immune system. This system has three different activating pathways and results in the formation of a membrane attack complex that ultimately causes target cell lysis.
Result and Discussion: In this review, we aimed to share information about the functioning of the complement system in the central nervous system and how it contributes to chronic neuroinflammation that leads to neurodegenerative disorders such as Alzheimer’s disease.
Kaynakça
- 1. Emmerling, M.R., Watson, M.D., Raby, C.A., Spiegel, K. (2000). The role of complement in Alzheimer's disease pathology. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1502(1), 158-171. [CrossRef]
- 2. Veerhuis, R., Nielsen, H.M., Tenner, A.J. (2011). Complement in the brain. Molecular Immunology, 48(14), 1592-1603. [CrossRef]
- 3. Crehan, H., Hardy, J., Pocock, J. (2012). Microglia, Alzheimer's disease, and complement. International Journal of Alzheimer's disease, 2012, 983640. [CrossRef]
- 4. Ueno, M., Chiba, Y., Murakami, R., Matsumoto, K., Kawauchi, M., Fujihara, R. (2016). Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions. Brain Tumor Pathology, 33(2), 89-96. [CrossRef]
- 5. Morgan, B.P. (2018). Complement in the pathogenesis of Alzheimer's disease. Seminars in Immunopathology, 40(1), 113-124. [CrossRef]
- 6. Montagne, A., Barnes, S.R., Sweeney, M.D., Halliday, M.R., Sagare, A.P., Zhao, Z., Toga, A.W., Jacobs, R. E., Liu, C.Y., Amezcua, L., Harrington, M.G., Chui, H.C., Law, M., Zlokovic, B.V. (2015). Blood-brain barrier breakdown in the aging human hippocampus. Neuron, 85(2), 296-302. [CrossRef]
- 7. Varatharaj, A., Galea, I. (2017). The blood-brain barrier in systemic inflammation. Brain, Behavior, and Immunity, 60, 1-12. [CrossRef]
- 8. Takeda, S., Sato, N., Morishita, R. (2014). Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Frontiers in Aging Neuroscience, 6, 171. [CrossRef]
- 9. McGeer, E.G., McGeer, P.L. (1998). The importance of inflammatory mechanisms in Alzheimer disease. Experimental Gerontology, 33(5), 371-378. [CrossRef]
- 10. Shinjyo, N., Kagaya, W., Pekna, M. (2021). Interaction between the complement system and ınfectious agents-A potential mechanistic link to neurodegeneration and dementia. Frontiers in Cellular Neuroscience, 15, 710390. [CrossRef]
- 11. Mapunda, J.A., Tibar, H., Regragui, W., Engelhardt, B. (2022). How does the immune system enter the brain? Frontiers in Immunology, 13, 805657. [CrossRef]
- 12. Shah, A., Kishore, U., Shastri, A. (2021). Complement system in Alzheimer's disease. International Journal of Molecular Sciences, 22(24), 13647. [CrossRef]
- 13. WHO (World Health Organization) web site. (2023). Dementia. Available online: https://www.who.int/news-room/fact sheets/detail/dementia. Erişim tarihi: 27.03.2023.
- 14. Kumar, P.J., Clark, M. (2011). Kumar & Clark’s Clinical Medicine, Saunders Elsevier, Edinburgh.
- 15. Tenner A.J. (2020). Complement-mediated events in Alzheimer’s disease: Mechanisms and potential therapeutic targets. Journal of Immunology, 204(2), 306-315. [CrossRef]
- 16. Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S.G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., Cooper, C., Fox, N., Gitlin, L.N., Howard, R., Kales, H.C., Larson, E. B., Ritchie, K., Rockwood, K., Sampson, E.L., Samus, Q., Schneider, L.S., Selbæk, G., Teri, L., Mukadam, N. (2017). Dementia prevention, intervention, and care. Lancet, 390(10113), 2673-2734. [CrossRef]
- 17. Sala Frigerio, C., Wolfs, L., Fattorelli, N., Thrupp, N., Voytyuk, I., Schmidt, I., Mancuso, R., Chen, W.T., Woodbury, M.E., Srivastava, G., Möller, T., Hudry, E., Das, S., Saido, T., Karran, E., Hyman, B., Perry, V. H., Fiers, M., De Strooper, B. (2019). The major risk factors for Alzheimer’s disease: Age, sex, and genes modulate the microglia response to Aβ plaques. Cell Reports, 27(4), 1293-1306. [CrossRef]
- 18. Shastri, A., Bonifati, D.M., Kishore, U. (2013). Innate immunity and neuroinflammation. Mediators of inflammation, 2013, 342931. [CrossRef]
- 19. Liu, Y.P., Lin, H.I., Tzeng, S.F. (2005). Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. Brain Research, 1054(2), 152-158. [CrossRef]
- 20. Harms, A.S., Lee, J.K., Nguyen, T.A., Chang, J., Ruhn, K.M., Treviño, I., Tansey, M.G. (2012). Regulation of microglia effector functions by tumor necrosis factor signaling. Glia, 60(2), 189-202. [CrossRef]
- 21. Jimenez, S., Baglietto-Vargas, D., Caballero, C., Moreno-Gonzalez, I., Torres, M., Sanchez-Varo, R., Ruano, D., Vizuete, M., Gutierrez, A., Vitorica, J. (2008). Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's disease: Age-dependent switch in the microglial phenotype from alternative to classic. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 28(45), 11650-11661. [CrossRef]
- 22. Zhang, L., Dong, Z.F., Zhang, J.Y. (2020). Immunomodulatory role of mesenchymal stem cells in Alzheimer's disease. Life Sciences, 246, 117405. [CrossRef]
- 23. Yong, H.Y.F., Rawji, K.S., Ghorbani, S., Xue, M., Yong, V.W. (2019). The benefits of neuroinflammation for the repair of the injured central nervous system. Cellular & Molecular Immunology, 16(6), 540-546. [CrossRef]
- 24. Lo, M.W., Woodruff, T.M. (2020). Complement: Bridging the innate and adaptive immune systems in sterile inflammation. Journal of Leukocyte Biology, 108(1), 339-351. [CrossRef]
- 25. Aisen, P.S., Cummings, J., Jack, C.R., Jr, Morris, J.C., Sperling, R., Frölich, L., Jones, R.W., Dowsett, S.A., Matthews, B.R., Raskin, J., Scheltens, P., Dubois, B. (2017). On the path to 2025: Understanding the Alzheimer's disease continuum. Alzheimer's Research & Therapy, 9(1), 60. [CrossRef]
- 26. Bonifati, D.M., Kishore, U. (2007). Role of complement in neurodegeneration and neuroinflammation. Molecular Immunology, 44(5), 999-1010. [CrossRef]
- 27. Schartz, N.D., Tenner, A.J. (2020). The good, the bad, and the opportunities of the complement system in neurodegenerative disease. Journal of Neuroinflammation, 17(1), 354. [CrossRef]
- 28. Velazquez, P., Cribbs, D.H., Poulos, T.L., Tenner, A.J. (1997). Aspartate residue 7 in amyloid beta-protein is critical for classical complement pathway activation: implications for Alzheimer's disease pathogenesis. Nature Medicine, 3(1), 77-79. [CrossRef]
- 29. Shen, Y., Lue, L., Yang, L., Roher, A., Kuo, Y., Strohmeyer, R., Goux, W.J., Lee, V., Johnson, G.V., Webster, S.D., Cooper, N.R., Bradt, B., Rogers, J. (2001). Complement activation by neurofibrillary tangles in Alzheimer's disease. Neuroscience Letters, 305(3), 165-168. [CrossRef]
- 30. Tenner, A.J., Stevens, B., Woodruff, T.M. (2018). New tricks for an ancient system: Physiological and pathological roles of complement in the CNS. Molecular Immunology, 102, 3-13. [CrossRef]
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