NÖROİNFLAMASYON İLE BOZULMUŞ GLİKOZ METABOLİZMASI ARASINDAKİ İLİŞKİYE HASTALIK TEMELLİ BAKIŞ

Yıl 2024, , 132 - 136, 30.10.2024

Mehmet Akif Ovalı , Şevval Perçin

https://doi.org/10.61845/agrimedical.1527141

Öz

Nöroinflamasyon, Alzheimer Hastalığı, Parkinson Hastalığı, Huntington Hastalığı ve amiyotrofik lateral skleroz gibi birçok merkezi sinir sistemi bozukluğunun patogenezine önemli bir katkıda bulunur. Nöroinflamasyon, merkezi sinir sisteminin yabancı ajanlar, moleküller, metabolik aktiviteler veya çeşitli hastalıklar tarafından bozulmuş merkezi veya periferik anormalliklere karşı verdiği bağışıklık tepkisidir. Astroglia ve mikroglia aktivasyonu, nöroinflamasyonun ana tetikleyicileridir. Bu savunucu hücrelerin polarizasyon değişiklikleri, sinirsel davranış kadar vücut metabolizmasında da önemli roller oynar. Kan-beyin bariyeri, beyin parankimasının ilk savunucusu olarak bilinir. Nöroinflamasyon, kan-beyin bariyerinin bütünlüğünü bozar ve kan-beyin bariyerinin yıkılmasına neden olabilir. Glikoz, beynin ana enerji kaynağıdır ve glikoz alımı kan-beyin bariyeri aracılığıyla sağlanır. Bozulmuş glikoz metabolizması, beyin fonksiyonları üzerinde zararlı etkilere sahip olabilir ve beyin bozukluklarına yol açabilir. Ayrıca, nöroinflamasyonun glikoz metabolizmasında önemli bir rol oynayabileceği öne sürülmüştür. Kan-beyin bariyerinin nöronlar, astroglia ve mikroglianın vasküler endotelyal hücrelerindeki dağılımı, glikozun beyin hücrelerine taşınmasına katkıda bulunur. Mikroglia ve astroglia polarizasyonu, nöroinflamasyonun altında yatan iki ana mekanizma olarak öne sürülmüştür. Nöroinflamasyon kaynaklı nörodejeneratif hastalıkların beyin insülin direnci ve bozulmuş beyin ve periferik glikoz metabolizması ile yakından ilişkili olduğu açıkça belirlenmiştir. Bununla birlikte, glikoz metabolizması bozuklukları ve mikroglia/astroglia polarizasyonu hakkında yeterli bilgi bulunmamaktadır. Bu derlemede, en yaygın nörolojik hastalıklarla birlikte nöroinflamasyon ve glikoz metabolizması ile mikroglia/astroglia polarizasyonunun glikoz metabolizması üzerindeki olası etkilerini özetledik.

Anahtar Kelimeler

Nöroinflamasyon, glikoz metabolizması, mikroglia, astrosit, nörodejenerasyon, nörolojik bozukluklar

A DISEASE-BASED PERSPECTIVE OF THE RELATIONSHIP BETWEEN NEUROINFLAMMATION AND IMPAIRED GLUCOSE METABOLISM

Öz

Neuroinflammation is a significant contributor to the pathogenesis of several central nervous system disorders including Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, and amyotrophic lateral sclerosis. Neuroinflammation is the immune response of the central nervous system against central or peripheral abnormalities disturbed by foreign agents, molecules, metabolic activities, or various diseases. Astrocytes and microglia activation are the main activators of neuroinflammation. The polarization changes of these defender cells have some key roles in bodily metabolism as much as neuronal behavior. The blood-brain barrier is known as the first defender of brain parenchyma. Neuroinflammation disrupts blood-brain barrier integrity and may cause blood-brain barrier breakdown. Glucose is the main energy source of brain and glucose uptake is achieved through the blood-brain barrier. Altered glucose metabolism may have detrimental effects on brain functions and may cause brain disorders. Also, it has been suggested that neuroinflammation may have crucial roles in glucose metabolism. The distribution of the blood-brain barrier in vascular endothelial cells of neurons, astrocytes, and microglia contributes to the transport of glucose to the cells of brain. Microglia and astrocyte polarization are suggested as the two main underlying mechanisms in neuroinflammation. It’s obviously determined that neuroinflammation-caused neurodegenerative diseases are tightly linked with the brain insulin resistance and disrupted cerebral and peripheral glucose metabolism. However, there is lacking knowledge about glucose metabolism deficiencies and microglia/astrocyte polarization. Herein this review, we summarized the neuroinflammation and glucose metabolism with the most common neurological diseases and the possible effects of microglia/astrocyte polarization on glucose metabolism.

Anahtar Kelimeler

Neuroinflammation, glucose metabolism, microglia, astrocyte, neurodegeneration, neurological disorders

Kaynakça

• 1. Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G. Neuroinflammation pathways: a general review. Int J Neurosci. 2017;127(7):624-33.
• 2. Aksöz E. The Role of Neuroinflammation in Epileptogenesis and Antiepileptogenic Therapy Targets Directed to Neuroinflammation. SDÜ Sağlık Bilimleri Dergisi. 2018;9(2):130-5.
• 3. Avola R, Furnari AG, Graziano ACE, Russo A, Cardile V. Management of the Brain: Essential Oils as Promising Neuroinflammation Modulator in Neurodegenerative Diseases. Antioxidants (Basel). 2024;13(2):178.
• 4. Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma D. Neuroinflammation: the role and consequences. Neurosci Res. 2014;79:1-12.
• 5. Kalsbeek MJ, Mulder L, YiCX. Microglia energy metabolism in metabolic disorder. Mol Cell Endocrinol. 2016;438:27–35.
• 6. Yang R, Yang B, Liu W et al. Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes. J Neuroinflammation. 2023;20(1):173.
• 7. García-Cáceres C, Balland E, Prevot V et al. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nat Neurosci. 2019;22(1):7-14.
• 8. González-García I, García-Cáceres C. Hypothalamic Astrocytes as a Specialized and Responsive Cell Population in Obesity. Int J Mol Sci. 2021;22(12):6176.
• 9. Falkowska A, Gutowska I, Goschorska M et al. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism. Int J Mol Sci. 2015;16(11):25959-81.
• 10. Dai C, Tan C, Zhao L et al. Glucose metabolism impairment in Parkinson's disease. Brain Res Bull. 2023;199:110672.
• 11. Zhang S, Lachance BB, Mattson MP, Jia X. Glucose metabolic crosstalk and regulation in brain function and diseases. Prog Neurobiol. 2021;204:102089.
• 12. Khan MA, Schultz S, Othman A et al. Hyperglycemia in Stroke Impairs Polarization of Monocytes/Macrophages to a Protective Noninflammatory Cell Type. J Neurosci. 2016;36(36):9313-25.
• 13. Ardanaz CG, Ramírez MJ, Solas M. Brain Metabolic Alterations in Alzheimer's Disease. Int J Mol Sci. 2022;23(7):3785.
• 14. Bahçeli̇ Ö, Şenol ŞP, Tunçtan B. Experimental Models in Neuroinflammatory Diseases: Systematic Review. J Lit Pharm Sci. 2021;10(2):153-65.
• 15. Kurban MG, Şentürk M. The Role of Cholinesterase Inhibitors on the Alzheimer Treatment. Ağrı Med J. 2024;(1):42-45.
• 16. Miao, J., Ma, H., Yang, Y., Liao, Y., Lin, C., Zheng, J., Yu, M., & Lan, J. Microglia in Alzheimer's disease: pathogenesis, mechanisms, and therapeutic potentials. Front Aging Neurosci. 2023;15:1201982.
• 17. Kim, S., Sharma, C., Jung, U. J., & Kim, S. R. Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease. Biomedicines, 2023;11(5):1383.
• 18. Weise CM, Chen K, Chen Y et al. Left lateralized cerebral glucose metabolism declines in amyloid-β positive persons with mild cognitive impairment. Neuroimage Clin. 2018;20:286-96.
• 19. Hsieh CF, Liu CK, Lee CT et al. Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation. Sci Rep. 2019;9:840.
• 20. Sędzikowska A, Szablewski L. Insulin and Insulin Resistance in Alzheimer’s Disease. Int J Mol Sci. 2021;22(18):9987.
• 21. Shah K, Desilva S, Abbruscato T. The role of glucose transporters in brain disease: diabetes and Alzheimer’s Disease. Int J Mol Sci. 2012;13(10):12629-55.
• 22. Xu XJ, Yang MS, Zhang B et al. Glucose metabolism: A link between traumatic brain injury and Alzheimer’s disease. Chin J Traumatol. 2021;24(1):5-10.
• 23. Manoharan S, Guillemin GJ, Abiramasundari RS et al. The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review. Oxid Med Cell Longev. 2016:8590578.
• 24. Cheong, JLY, de Pablo-Fernandez, E, Foltynie, T, Noyce, AJ. The Association Between Type 2 Diabetes Mellitus and Parkinson's Disease. J Parkinsons Dis. 2020;10(3):775–789.
• 25. Liu M, Jiao Q, Du X et al. Potential Crosstalk Between Parkinson's Disease and Energy Metabolism. Aging Dis. 2021;12(8):2003–2015.
• 26. Podolsky S, Leopold NA. Abnormal glucose tolerance and arginine tolerance tests in Huntington’s disease. Gerontology. 1977;23:55–63.
• 27. Farrer LA. Diabetes mellitus in Huntington disease. Clin Genet. 1985;27:62–67.
• 28. Lalić NM, Marić J, Svetel M et al. Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion. Arch Neurol. 2008;65:476–480.
• 29. Singh A, Agrawal N. Metabolism in Huntington's disease: a major contributor to pathology. Metab Brain Dis. 2022;37(6):1757–1771.
• 30. Nambron R, Silajdžić E, Kalliolia E et al. A Metabolic Study of Huntington's Disease. PloS one. 2016;11(1):e0146480.
• 31. Singh A, & Agrawal, N. Metabolism in Huntington's disease: a major contributor to pathology. Metab Brain Dis. 2022;37(6):1757–1771.
• 32. Pradat PF, Bruneteau G, Gordon PH et al. Impaired glucose tolerance in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11(1-2):166-71.
• 33. Tefera TW, Steyn FJ, Ngo ST, Borges K. CNS glucose metabolism in Amyotrophic Lateral Sclerosis: a therapeutic target? Cell Biosci. 2021;11(1):14.
• 34. Nelson AT, Trotti D. Altered Bioenergetics and Metabolic Homeostasis in Amyotrophic Lateral Sclerosis. Neurotherapeutics. 2022;19(4):1102–1118.
• 35. Raghunathan R, Turajane K, Wong LC. Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease. Int J Mol Sci. 2022;23(16):9299.
• 36. Ahonen, S, Nitschke, S, Grossman, TR, Kordasiewicz, H, Wang, P, Zhao, X, Guisso, DR, Kasiri, S, Nitschke, F, Minassian, BA. Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease. Brain. 2021;144(10):2985–2993.
• 37. Duran, J, Tevy, MF, Garcia-Rocha, M, Calbó, J, Milán, M, Guinovart, JJ. Deleterious effects of neuronal accumulation of glycogen in flies and mice. EMBO Mol Med. 2012;4(8):719–729.
• 38. Brewer, MK, Torres, P, Ayala, V, Portero-Otin, M, Pamplona, R, Andrés-Benito, P, Ferrer, I, Gentry, MS, Guinovart, JJ, Duran, J. Glycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis. J Neurochem. 2024;168(5):744–759.