EXOSOMES AND ITS RELATIONSHIP WITH NEURODEGENERATIVE DISEASES

Öz

The new perspective that nanotechnology has created in the field of health and science has inspired the field of biotechnology by allowing DNA molecules to be examined developed and produced by special methods. With nanotechnological applications especially in drug delivery systems, the pharmacokinetics, pharmacodynamics and therapeutic indices of drugs have been improved, the drug has been released continuously and in a controlled manner, thereby reducing the side effects of the drug and it is aimed to show an effective bioavailability in targeted tissues and cells. With the advances achieved with the effective use of nanosized structures in biotechnology, the vesicular structures secreted from all kinds of cells and called extracellular vesicles have enabled exciting studies in the field of medicine and biology. Studies using transmembrane receptors of biomolecules and extracellular vesicles as communication tools in genetic information transfer have gained importance in recent years. For this reason, extracellular vesicles, which are now considered as natural liposomes of biotechnology, have gained importance in the diagnosis and treatment of diseases due to their biocompatibility and their easy availability.

Anahtar Kelimeler

• Exosome
• nanotechnology
• neurodegenerative diseases.

EKSOZOMLAR VE NÖRODEJENERATİF HASTALIKLARLA İLİŞKİSİ

Öz

Nanoteknolojinin sağlık ve fen bilimleri alanında oluşturduğu yeni bakış açısı, DNA moleküllerinin özel yöntemlerle incelenmesine, geliştirilmesine ve üretilmesine olanak sağlayarak, biyoteknoloji bilim dalına esin kaynağı olmuştur. Özellikle ilaç dağıtım sistemlerinde nanoteknolojik uygulamalar ile ilaçların farmakokinetiği, farmakodinamiği ve terapötik endeksleri geliştirilmiş, ilacın sürekli ve kontrollü salınımı sağlanmış ve bu sayede ilacın yan etkileri azaltılarak hedeflenen doku ve hücrelerde etkin bir biyo-yararlanım göstermesi hedeflenmiştir. Nano boyuttaki yapıların biyoteknolojideki etkin kullanımları ile elde edilen gelişmelerle birlikte, her türlü hücreden salgılanan ve hücre dışı veziküller olarak adlandırılan veziküler yapılar, tıp ve biyoloji alanında heyecan verici çalışmaların yapılmasına olanak sağlamıştır. Biyo-moleküllerin transmembran reseptörleri ve genetik bilgi aktarımında iletişim aracı olarak hücre dışı veziküllerin kullanıldığı çalışmalar son yıllarda oldukça önem kazanmıştır. Bu nedenle şimdilerde biyoteknolojinin doğal lipozomları olarak nitelendirilen hücre dışı veziküller, hastalıkların tanı ve tedavisinde hem biyo-uyumlulukları hem de kolay elde edilebilir olmaları sebebiyle oldukça önem kazanmıştır.

Anahtar Kelimeler

• Eksozom
• Nörodejeneratif hastalıklar
• Nanoteknoloji

Kaynakça

1. 1. Ersöz, Ezgi, Osman Burak Can, and Selim Uzunoğlu. "Eksozomların Kanserdeki Rolü." Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 2016; 3.1: 144-152.
2. 2. Bo Yu, Xiaomin Zhang, Xiaorong Li, Exosomes Derived from Mesenchymal Stem Cells, Int. J. Mol. Sci. 2014; 15: 4142-4157.
3. 3. JS. Schorey, S. Bhatnagar .Exosome function: from tumor immunology to pathogen biology. Traffic, 2008; 9: 871-881.
4. 4. J.Lötvall, A. F. Hill, F. Hochberg, E. I. Buzás, D. D. Vizio, C. Gardiner,Y. S. Gho, I. V. Kurochkin, S. Mathivanan, P.Quesenberry, S. Sahoo, H. Tahara, M. H. Wauben, K. W. Witwer, C. Théry, Minimal Experimental Requirements For Definition of Extracellular Vesicles and Their Functions: A Position Statement From The International Society For Extracellular Vesicles, Journal of Extracellular Vesicles, 2014; 3: 26913.
5. 5. Xu W, Yang Z, Lu N. From pathogenesis to clinical application: insights into exosomes as transfer vectors in cancer. J Exp Clin Cancer Res. 2016; 35: 156-168.
6. 6. M. Tkach, C. Thery .Communication by extracellular vesicles: Where we are and where we need to go. Cell. 2016; 164: 1226–32.
7. 7. Y. Yuana, A. Sturk, R. V. Extracellular vesicles in physiological and pathological conditions. Blood Rev. 2013; 27: 31-9.
8. 8. A. Sharma, Z. Khatun, A. Shiras. Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy. Nanomedicine, 2016; 11: 421-437.

9. 9. EJ.Bunggulawa, W. Wang, T., N. Wang, C. Durkan, Y. Wang, G. Wang, Recent advancements in the use of exosomes as drug delivery systems, J Nanobiotechnol.2018;16: 81
10. 10. SA. Melo, LB. Luecke, C. Kahlert, AF. Fernandez, ST. Gammon. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature, 2015; 523: 177-U82.
11. 11. M. W. Welker, D. Reichert, S. Susser et al., “Soluble serum CD81 is elevated in patients with chronic hepatitis c and correlates with alanine aminotransferase serum activity,” PLoS ONE.2012; 7:2, Article ID e30796.
12. 12. M. Logozzi, A. de Milito, L. Lugini et al., “High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients,” PLoS ONE.2009; 4:4, Article ID e5219.
13. 13. H. Zhou, A. Cheruvanky, X. Hu et al., “Urinary exosomal transcription factors, a new class of biomarkers for renal disease,” Kidney International. 2008; 74:5, 613–621.
14. 14. S. Khan, HF. Bennit, D. Turay, M. Perez, S. Mirshahidi, Y. Yuan. Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer. 2014; 14: 176.
15. 15. R. Ge, E. Tan, S. Sharghi-Namini, HH. Asada. Exosomes in Cancer Microenvironment and Beyond: have We Overlooked These Extracellular Messengers? Cancer Microenviron. 2012; 5: 323-332.
16. 16. L. Mincheva-Nilsson, V. Baranov, O. Nagaeva, E. Dehlin. Isolation and characterization of exosomes from cultures of tissue explants and cell lines. Curr Protoc Immunol. 2016; 115: 14 42 11–14 42 21.
17. 17. H. Xin, F. Wang, Y. Li, QE. Lu, WL. Cheung, Y. Zhang, ZG. Zhang, M. Chopp, Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from microRNA 133b-overexpressing multipotent mesenchymal stromal cells. Cell Transplant. 2017; 26 (2) :243–257.
18. 18. D. Sun, X. Zhuang, X. Xiang, Y. Liu, S. Zhang, C. Liu, S. Barnes, W. Grizzle, D. Miller, H.G. Zhang, A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes, Mol. Ther. 2010; (18): 1606–1614.
19. 19. X. Zhuang, X. Xiang, W. Grizzle, D. Sun, S. Zhang, R.C. Axtell, S. Ju, J. Mu, L. Zhang, L. Steinman, D. Miller, H.G. Zhang, Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain, Mol. Ther. 2011; 19: 1769–1779.a
20. 20. Lai CP, Breakefield XO. Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Front Physiol. 2012; 3: 228.
21. 21. Yuyama K, Sun H, Mitsutake S, et al. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-beta by microglia. J BiolChem. 2012; 287: 10977–10989.
22. 22. Fevrier B, Vilette D, Laude H, et al. Exosomes: a bubble ride for prions? Traffic, 2005; 6: 10–17.
23. 23. Sardi F1, Fassina L,Venturini L, et al. Alzheimer’s disease, autoimmunity and inflammation. The good, the bad and the ugly. Autoimmun Rev. 2011; 11 (2): 149–153. PMID: 23930978.
24. 24. Wang G, Dinkins M, He Q, et al. Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4):potential mechanism of apoptosis induction in Alzheimer disease (AD). J BiolChem. 2012; 287: 21384–21395.
25. 25. Bulloj A, Leal MC, Xu H, et al. Insulin-degrading enzyme sorting in exosomes: a secretory pathway for a key brain amyloid-beta degrading protease. J AlzheimersDis. 2010;19:79–95.
26. 26. L. Rajendran, M. Honsho, T. R. Zahn et al., Alzheimer's disease β-amyloid peptides are released in association with exosomes, Proceedings of the National Academy of Sciences of the United States of America, 2006; 103 (30): 11172–11177.
27. 27. S. Saman, W. Kim, M. Raya et al., “Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease,” Journal of Biological Chemistry. 2012; 287 (6): 3842–3849.
28. 28. Egre-Abarrategui J, Wade-Martins R. Parkinson disease, LRRK2 and the endocytic-autophagic pathway. Autophagy. 2009; 5: 1208–1210.
29. 29. Shin N, Jeong H, Kwon J, et al. LRRK2 regulates synaptic vesicle endocytosis. ExpCellRes. 2008; 314: 2055–2065.
30. 30. Giasson BI, Forman MS, Higuchi M, et al. Initiation and synergistic fibrillization of tau and alpha-synuclein. Science. 2003; 300: 636–640.
31. 31. L. Yuan, JY. Li, Exosomes in Parkinson’s Disease: Current Perspectives and Future Challenges. ACS Chem. Neurosci. 2019; 10 (2): 964–972.
32. 32. Karagkouni A1, Alevizos M, Theoharides TC. Effect of stress on brain inflammation and multiple sclerosis. Autoimmun Rev. 2013; 12 (10): 947–953.
33. 33. Keller A, Leidinger P, Lange J, et al. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsingremitting disease from healthy controls. PLoS One. 2009; 4: e7440.
34. 34. Pusic AD, Kraig RP. Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination. GLIA. 2014; 62: 284–299.
35. 35. Dugas JC, Cuellar TL, Scholze A, et al. Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron. 2010; 65: 597–611.
36. 36. Shin D, Shin JY, McManus MT, et al. Dicer ablation in oligodendrocytes provokes neuronal impairment in mice. Ann Neurol. 2009; 66: 843–857.
37. 37. Pusic AD, Pusic KM, Clayton BL, et al. IFNgamma-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J Neuroimmunol. 2014; 266: 12–23.
38. 38. Aguzzi A, Heikenwalder M. Pathogenesis of prion diseases: current status and future outlook. Nat Rev Microbiol. 2006; 4: 765–775.
39. 39. Alais S, Simoes S, Baas D, et al. Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles. Biol Cell. 2008; 100: 603–615.
40. 40. Faure J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurons. Mol Cell Neurosci. 2006; 31: 642–648.
41. 41. Taylor DR, Hooper NM. The prion protein and lipid rafts. Mol Membr Biol. 2006; 23: 89–99.
42. 42. Banigan MG, Kao PF, Kozubek JA, et al. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS One. 2013; 8: e48814.
43. 43. Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res 2004; 64(19): 6892-9.
44. 44. Skog J, Wurdinger T, van RS, et al. Glioblastoma microvesicles trans port RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10: 1470–1476.
45. 45. Manterola L, Guruceaga E, Gallego Perez-Larraya J,et al. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro Oncol. 2014; 16: 520–527.
46. 46. Katakowski M, Buller B, Zheng X, et al. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett. 2013; 335: 201–204.
47. 47. Theoharides TC, Conti P, Economu M. Brain inflammation, neuropsychiatric disorders, and immunoendocrine effects of luteolin. J Clin Psychopharmacol. 2014; 34: 187– 189.