Experimed

GÖNDERBİLGİ
EnglishTürkçe

Derleme


DOI :10.26650/experimed.2019.19025   IUP :10.26650/experimed.2019.19025    Tam Metin (PDF)

Rifampisinin Nöronal Sağkalım Üzerine Etkileri

İlknur Yurtsever, Ebru Emekli Alturfan

Nörodejeneratif hastalıklar, merkezi sinir siteminde yanlış katlanmış proteinlerin çözünmeyen agregatlarının oluşumu ile karakterizedir. Bunlara örnek olarak; Alzheimer hastalığında β-amyloid protein ve Parkinson hastalığında α-sinüklein oluşumu verilebilir. Parkinson hastalığında α-sinüklein agregasyonuna ek olarak, oksidatif stress, mitokondri fonksiyon bozukluğu, inflamatuvar cevap, apoptoz gibi mekanizmaların hastalık sürecine katıldığı bilinmektedir. Bu hastalıkların altında yatan mekanizmalar tam olarak bilinmediği için, hastalığa ilişkin geliştirilen ilaçlar, hastalığı iyileştirmekten çok, hastalığın seyrini yavaşlatma eğilimindedir. Rifampisin insanlar tarafından sıkça kullanılan bir antibiyotiktir ve ağız yoluyla alındıktan sonra beyne kolaylıkla penetre olmaktadır. Rifampisinin in vivo ve in vitro hastalık modellerinde mitokondriyal oksidatif stresi baskıladığı, α-sinüklein fibrillerini ayrıştırdığı, inflamasyonu inhibe ettiğini gösteren çok sayıda çalışma mevcuttur. Biz bu çalışmada, rifampisinin nöronal korunumu üzerine raporlanan çalışmaları ve Parkinson hastalığı’nın patofizyolojik mekanizmaları üzerine rifampisinin etkilerini derledik. 

Anahtar Kelimeler: Parkinson hastalığı, rifampisin, α-Sinüklein, SUMOlasyon, inflamasyon, otofaji
DOI :10.26650/experimed.2019.19025   IUP :10.26650/experimed.2019.19025    Tam Metin (PDF)

The Effects of Rifampicin on Neuronal Survival

İlknur Yurtsever, Ebru Emekli Alturfan

Neurodegenerative diseases are characterized by the formation of insoluble aggregates of misfolded proteins in the central nervous system. The β-amyloid protein in Alzheimer's disease and α-synuclein formation in Parkinson's disease (PD) may be given as examples. In addition to α-synuclein accumulation in Parkinson's disease, mechanisms such as oxidative stress, dysfunction of mitochondria, inflammation response, and apoptosis are known to be involved in the disease process. Since the mechanisms underlying these diseases are partially known, the drugs developed are intended to slow the disease process rather than cure them. Rifampicin is an antibiotic commonly used in humans and known to easily penetrate into the brain after oral intake. Studies have shown that rifampicin suppresses mitochondrial oxidative stress, eliminates α-synuclein fibrils and inhibits inflammation in in vitro and in vivo disease models. In this study, we reviewed recent studies on the neuronal protection of rifampicin and the effects of rifampicin on the pathophysiological mechanisms of PD.

Anahtar Kelimeler: Parkinson’s disease, rifampicin, α-Synuclein, SUMOylation, inflammation, autophagy

PDF Görünüm

Referanslar

  • 1. Ambrosi G, Cerri S, Blandini F. A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. J Neural Transm 2014; 121: 849-59. [CrossRef] google scholar
  • 2. Giráldez-Pérez R, Antolín-Vallespín M, Muñoz M, Sánchez-Capelo A. Models of α-synuclein aggregation in Parkinson’s disease. Acta Neuropathol Commun 2014; 2: 176. doi: 10.1186/s40478-014-0176-9. [CrossRef] google scholar
  • 3. Blesa J, Trigo-Damas I, Quiroga-Varela A and Jackson-Lewis V R. Oxidative stress and Parkinson’s disease. Front Neuroanat 2015; 9: https://doi.org/10.3389/fnana.2015.00091 [CrossRef] google scholar
  • 4. Franco-Iborra S, Vila M, Perier C. The Parkinson disease mitochondrial hypothesis: where are we at? Neuroscientist 2016; 22: 266-77. [CrossRef] google scholar
  • 5. Vivekanantham S, Shah S, Dewji R, Dewji A, Khatri C, Ologunde R. Neuroinflammation in Parkinson’s disease: role in neurodegeneration and tissue repair. Int J Neurosci 2015; 125: 717-25. [CrossRef] google scholar
  • 6. Guerra de Souza AC, Prediger RD, Cimarosti H. SUMO-regulated mitochondrial function in Parkinson’s disease. J Neurochem 2016; 137: 673-86. [CrossRef] google scholar
  • 7. Bi W, Zhu L, Jing X, Zeng Z, Liang Y, Xu A, et al. Rifampicin improves neuronal apoptosis in LPS-stimulated co-cultured BV2 cells through inhibition of the TLR-4 pathway. Mol Med Rep 2014; 10: 1793-9. [CrossRef] google scholar
  • 8. Jing X, Shi Q, Bi W, Zeng Z, Liang Y, Wu X, et al. Rifampicin protects PC12 cells from rotenone-induced cytotoxicity by activating GRP78 via PERK-eIF2alpha-ATF4 pathway. PLoS One 2014; 9: doi: 10.1371/journal.pone.0092110.[CrossRef] google scholar
  • 9. Xu J, Wei C, Xu C, Bennett M C, Zhang G, Li F, et al. Rifampicin protects PC12 cells against MPP+-induced apoptosis and inhibits the expression of an alpha-synuclein multimer. Brain Res 2007; 1139: 220-5. [CrossRef] google scholar
  • 10. Bi W, Zhu L, Wang C, Liang Y, Liu J, Shi Q, et al. Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation. Brain Res 2011; 1395: 12-20. [CrossRef] google scholar
  • 11. Greenamyre JT, Betarbet R, Sherer TB. The rotenone model of Parkinson’s disease: genes, environment, and mitochondria. Parkinsonism Relat Disord 2003; 9 (Suppl 2): S59-S64. [CrossRef] google scholar
  • 12. Testa CM, Sherer TB, Greenamyre JT. Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Brain Res Mol Brain Res 2005; 134: 220-5. [CrossRef] google scholar
  • 13. Watanabe Y, Himeda T, Araki T. Mechanisms of MPTP toxicity and their implications for therapy of Parkinson’s disease. Med Sci Monit 2005; 11: 17-23. google scholar
  • 14. Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT. An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 2002; 22: 7006-15. [CrossRef] google scholar
  • 15. Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 2008; 1147: 37-52. [CrossRef] google scholar
  • 16. Tretter L, Sipos I, Adam-Vizi V. Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson’s disease. Neurochem Res 2004; 29: 569-77. [CrossRef] google scholar
  • 17. Zhu J, Chu CT. Mitochondrial dysfunction in Parkinson’s disease. J Alzheimers Dis 2010; 20 (Suppl 2): S325-S34. [CrossRef] google scholar
  • 18. Tobo’n-Velasco JC, Carmona-Aparicio L, Ali SF, Santamarı’a A. Biomarkers of cell damage induced by oxidative stress in Parkinson’s disease and related models. Cent Nerv Syst Agents Med Chem 2010; 10: 278-86. [CrossRef] google scholar
  • 19. Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S. Role of mitochondria in toxic oxidative stress. Mol Interv 2005; 5: 94-111. [CrossRef] google scholar
  • 20. Beal MF. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 1992; 31: 119-30. [CrossRef] google scholar
  • 21. Adams JD Jr, Chang ML, Klaidman L. Parkinson’s disease-redox mechanisms. Curr Med Chem 2001; 8: 809-14. [CrossRef] google scholar
  • 22. Steele MA, Burk RF, DesPrez RM. Toxic hepatitis with isoniazid and rifampin. A meta-analysis. Chest 1991; 99: 465-71. [CrossRef] google scholar
  • 23. Xu B, Tang X, Chen J, Wu H, Chen W, Chen L. Rifampicin induces clathrin-dependent endocytosis and ubiquitin-proteasome degradation of MRP2 via oxidative stress-activated PKC-ERK/JNK/p38 and PI3K signaling pathways in HepG2 cells. Acta Pharmacol Sin 2019; doi: 10.1038/s41401-019-0266-0. [CrossRef] google scholar
  • 24. Oida Y, Kitaichi K, Nakayama H, Ito Y, Fujimoto Y, Shimazawa M, Nagai H, Hara H. Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain. Brain Res 2006; 1082: 196- 204. [CrossRef] google scholar
  • 25. Bo¨ttcher T, Gerber J, Wellmer A, Smirnov AV, Fakhrjanali F, Mix E, et al. Rifampin reduces production of reactive oxygen species of cerebrospinal fluid phagocytes and hippocampal neuronal apoptosis in experimental Streptococcus pneumoniae meningitis. J Infect Dis 2000; 181: 2095-8. [CrossRef] google scholar
  • 26. Chen S, Sun Y, Zeng Z, Tao E. Rifampicin inhibits apoptosis in rotenone-induced differentiated PC12 cells by ameliorating mitochondrial oxidative stress. Neural Regen Res 2010; 5: 251-6. google scholar
  • 27. Zhang J, Culp ML, Craver JG, Darley-Usmar V. Mitochondrial function and autophagy: integrating proteotoxic, redox, and metabolic stress in Parkinson’s disease. J Neurochem. 2018; 144: 691-709. [CrossRef] google scholar
  • 28. Bi W, Zhu L, Jing X, Zeng Z, Liang Y, Xu A, et al. Rifampicin improves neuronal apoptosis in LPS-stimulated cocultured BV2 cells through inhibition of the TLR-4 pathway. Mol Med Rep 2014; 10: 1793-9. [CrossRef] google scholar
  • 29. Yang S, Xia C, Li S, Du L, Zhang L, Zhou R. Defective mitophagy driven by dysregulation of rheb and KIF5B contributes to mitochondrial reactive oxygen species (ROS)-induced nod-like receptor 3 (NLRP3) dependent proinflammatory response and aggravates lipotoxicity. Redox Biol 2014; 3: 63-71. [CrossRef] google scholar
  • 30. Bi W, Jing X, Zhu L, Liang Y, Liu J, Yang L, et al. Inhibition of 26S protease regulatory subunit 7 (MSS1) suppresses neuroinflammation. PLoS One 2012; 7: doi: 10.1371/journal.pone.0036142. [CrossRef] google scholar
  • 31. Liang Y, Zhou T, Chen Y, Lin D, Jing X, Peng S, et al. Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy. Neurotoxicology 2017; 63: 137-45. [CrossRef] google scholar
  • 32. Giordano S, Dodson M, Ravi S, Redmann M, Ouyang X, Darley Usmar VM, et al. Bioenergetic adaptation in response to autophagy regulators during rotenone exposure. J Neurochem 2014; 131: 625-33. [CrossRef] google scholar
  • 33. Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J Cell Sci 2007; 120: 4155-66. [CrossRef] google scholar
  • 34. Forno LS. Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 1996; 55: 259-72. [CrossRef] google scholar
  • 35. Martin FL, Williamson SJ, Paleologou KE, Allsop D, El-Agnaf OM. Alpha-synuclein and the pathogenesis of Parkinson’s disease. Protein Pept Lett 2004; 11: 229-37. [CrossRef] google scholar
  • 36. Bennett MC. The role of alpha-synuclein in neurodegenerative diseases. Pharmacol Ther 2005; 105: 311-31. [CrossRef] google scholar
  • 37. Lee SJ. alpha-Synuclein aggregation: a link between mitochondrial defects and Parkinson’s disease? Antioxid Redox Signal 2003; 3: 337-48. [CrossRef] google scholar
  • 38. Couch Y, Alvarez-Erviti L, Sibson NR, Wood MJA, Anthony DC. The acute inflammatory response to intranigral-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation. J Neuroinflamm 2011; 8: doi: 10.1186/1742-2094-8-166. [CrossRef] google scholar
  • 39. Acuña L, Hamadat S, Corbalán NS, González-Lizárraga F, Dos-Santos-Pereira M, Rocca J, et al. Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates. Cells 2019; 8: doi: 10.3390/cells8080776. [CrossRef] google scholar
  • 40. Gustot A, Gallea, JI, Sarroukh R, Celej MS, Ruysschaert J-M, Raussens V. Amyloid fibrils are the molecular trigger of inflammation in Parkinson’s disease. Biochem J 2015; 471: 323-33. [CrossRef] google scholar
  • 41. Hoffmann A, Ettle B, Bruno A, Kulinich A, Hoffmann AC, von Wittgenstein J, et al. Alpha-synuclein activates BV2 microglia dependent on its aggregation state. Biochem Biophys Res Commun 2016; 479: 881-6. [CrossRef] google scholar
  • 42. Gareau JR, Lima CD. The SUMO pathway: emerging mechanisms that shape specificity, conjugation, and recognition. Nat Rev Mol Cell Biol 2010; 11: 861-71. [CrossRef] google scholar
  • 43. Eckermann K. SUMO and Parkinson’s Disease. NeuroMolecular Med 2013; 15: 737-59. [CrossRef] google scholar
  • 44. Dohmen RJ. SUMO protein modification. Biochim. Biophys. Acta 2004; 1695, 113-131. [CrossRef] google scholar
  • 45. Hay RT. SUMO: a history of modification. Mol Cell 2005; 18: 1-12. [CrossRef] google scholar
  • 46. Silveirinha V, Stephens GJ, Cimarosti H. Molecular targets underlying SUMO-mediated neuroprotection in brain ischemia. J Neurochem 2013; 127: 580-91. [CrossRef] google scholar
  • 47. Wilkinson KA, Nakamura Y, Henley JM. Targets and consequences of protein SUMOylation in neurons. Brain Res Rev 2010; 64: 195-212. [CrossRef] google scholar
  • 48. Luo J, Ashikaga E, Rubin PP, Heimann MJ, Hildick KL, Bishop P, et al. Receptor trafficking and the regulation of synaptic plasticity by SUMO. Neuromolecular Med 2013; 15: 692-706. [CrossRef] google scholar
  • 49. Anckar J, Sistonen L. SUMO: getting it on. Biochem Soc Trans 2007; 35: 1409-13. [CrossRef] google scholar
  • 50. Henley JM, Craig TJ and Wilkinson KA. Neuronal SUMOylation: mechanisms, physiology, and roles in neuronal dysfunction. Physiol Rev 2014; 94: 1249-85. [CrossRef] google scholar
  • 51. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997; 388: 839-40. [CrossRef] google scholar
  • 52. Kim YM, Jang WH, Quezado MM, Oh Y, Chung KC, Junn E, et al. Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation. J Neurol Sci 2011; 307: 157-61. [CrossRef] google scholar
  • 53. Krumova P, Meulmeester E, Garrido M, Tirard M, Hsiao HH, Bossis G, et al. Sumoylation inhibits a-synuclein aggregation and toxicity. J Cell Biol 2011; 194: 49-60. [CrossRef] google scholar
  • 54. Lin D, Jing X, Chen Y, Liang Y, Lei M, Peng S, et al. Rifampicin pre-treatment inhibits the toxicity of rotenone-induced PC12 cells by enhancing sumoylation modification of α-synuclein. Biochem Biophys Res Commun 2017; 485: 23-9. [CrossRef] google scholar
  • 55. Konrad P, Stenberg P. Rifampicin quinone is an immunosuppressant, but not rifampicin itself. Clin Immunol Immunopathol 1988; 46: 162-6. [CrossRef] google scholar
  • 56. Li J, Zhu M, Rajamani S, Uversky VN, Fink AL. Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils. Chem Biol 2004; 11: 1513-21. [CrossRef] google scholar
  • 57. Bi W, Zhu L, Jing X, Liang Y, Tao E. Rifampicin and Parkinson’s disease. Neurol Sci 2013; 34: 137-41. [CrossRef] google scholar

Atıflar

Biçimlendirilmiş bir atıfı kopyalayıp yapıştırın veya seçtiğiniz biçimde dışa aktarmak için seçeneklerden birini kullanın


DIŞA AKTAR



APA

Yurtsever, İ., & Emekli Alturfan, E. (0001). Rifampisinin Nöronal Sağkalım Üzerine Etkileri. Experimed, 9(3), 138-142. https://doi.org/10.26650/experimed.2019.19025


AMA

Yurtsever İ, Emekli Alturfan E. Rifampisinin Nöronal Sağkalım Üzerine Etkileri. Experimed. 0001;9(3):138-142. https://doi.org/10.26650/experimed.2019.19025


ABNT

Yurtsever, İ.; Emekli Alturfan, E. Rifampisinin Nöronal Sağkalım Üzerine Etkileri. Experimed, [Publisher Location], v. 9, n. 3, p. 138-142, 0001.


Chicago: Author-Date Style

Yurtsever, İlknur, and Ebru Emekli Alturfan. 0001. “Rifampisinin Nöronal Sağkalım Üzerine Etkileri.” Experimed 9, no. 3: 138-142. https://doi.org/10.26650/experimed.2019.19025


Chicago: Humanities Style

Yurtsever, İlknur, and Ebru Emekli Alturfan. “Rifampisinin Nöronal Sağkalım Üzerine Etkileri.” Experimed 9, no. 3 (Dec. 2024): 138-142. https://doi.org/10.26650/experimed.2019.19025


Harvard: Australian Style

Yurtsever, İ & Emekli Alturfan, E 0001, 'Rifampisinin Nöronal Sağkalım Üzerine Etkileri', Experimed, vol. 9, no. 3, pp. 138-142, viewed 22 Dec. 2024, https://doi.org/10.26650/experimed.2019.19025


Harvard: Author-Date Style

Yurtsever, İ. and Emekli Alturfan, E. (0001) ‘Rifampisinin Nöronal Sağkalım Üzerine Etkileri’, Experimed, 9(3), pp. 138-142. https://doi.org/10.26650/experimed.2019.19025 (22 Dec. 2024).


MLA

Yurtsever, İlknur, and Ebru Emekli Alturfan. “Rifampisinin Nöronal Sağkalım Üzerine Etkileri.” Experimed, vol. 9, no. 3, 0001, pp. 138-142. [Database Container], https://doi.org/10.26650/experimed.2019.19025


Vancouver

Yurtsever İ, Emekli Alturfan E. Rifampisinin Nöronal Sağkalım Üzerine Etkileri. Experimed [Internet]. 22 Dec. 2024 [cited 22 Dec. 2024];9(3):138-142. Available from: https://doi.org/10.26650/experimed.2019.19025 doi: 10.26650/experimed.2019.19025


ISNAD

Yurtsever, İlknur - Emekli Alturfan, Ebru. “Rifampisinin Nöronal Sağkalım Üzerine Etkileri”. Experimed 9/3 (Dec. 2024): 138-142. https://doi.org/10.26650/experimed.2019.19025



ZAMAN ÇİZELGESİ


Kabul11.11.2019

LİSANS


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


PAYLAŞ




İstanbul Üniversitesi Yayınları, uluslararası yayıncılık standartları ve etiğine uygun olarak, yüksek kalitede bilimsel dergi ve kitapların yayınlanmasıyla giderek artan bilimsel bilginin yayılmasına katkıda bulunmayı amaçlamaktadır. İstanbul Üniversitesi Yayınları açık erişimli, ticari olmayan, bilimsel yayıncılığı takip etmektedir.