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Neurodegenerative Diseases andSUMO

Yıl 2017, Cilt: 7 Sayı: 13, 59 - 70, 01.06.2017

Öz

In this review, it will be focused on the functions of SUMO (Small ubiquitin-like modifiers) proteins,

which are increasingly important in the pathophysiology of neurodegenerative diseases, on the disease

mechanisms. SUMO proteins play a crucial role in cellular processes. Recyclable covalent bonds created

by one of SUMOs’ (in mammals are defined as SUMO1, SUMO2, SUMO3, SUMO4) lysin remains from

target proteins and impairments in the sumoylation cycle are associated with many neurological disorders.

The identification of Huntingtin, ataxin-1, tau and α-synuclein as SUMO substrates leads to an

association between sumoylation and neurodegenerative diseases. In the scope of this review, firstly

informations about the SUMO proteins and sumoylation will be explained, thereafter informations on

relations between SUMO proteins and neurodegenerative diseases related to polyglutamine disorder

related diseases, neuronal intranuclear inclusion disease, Parkinson’s disease and Alzheimer’s disease

will be given.


Kaynakça

  • 1. Anderson DB, Zanella CA, Henley JM, Cimarotsi H. Sumoylation: Implications for Neurode-generative Diseases. Adv Exp Med Biol 2017; 963: 261-281. 2. Dorval V, Fraser PE. SUMO on the road to neurodegeneration. Biochim Biophys Acta 2007;1773: 694-706. 3. Li M, Guo D, Isales CM., Eizirik DL, Atkinson M, She JX, Wang CY. Sumo wrestling with type 1 diabetes. J Mol Med 2005; 83: 504- 513. 4. Wang CY, SHE JX. SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab Res Rev 2008; 24: 93–102. 5. Bohren KM, nadkarni V, Song JH, Gabbay KH,Owerbach, D. A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J Biol Chem 2004; 279: 27233–27238. 6. Rodriguez MS, Desterro JM, Lain S, Midgley CA, Lane DP, Hay RT. SUMO-1 modification activates the transcriptional response of p53. EMBO J 1999; 15: 6455-6461. 7. Tatham MH, Jaffray E, Vaughan OA, Desterro JMP, Botting CH, Naismith JH, Hay RT. Polymeric Chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/ SAE2 and Ubc9. J Bio Chem 2001; 276(38): 35368-35374. 8. Wilkinson KA, Henley JM. Mechanisms, regulation and consequences of protein SUMOylation Biochem J 2012; 428(2): 133-145. 9. Martin S, Wilkinson KA, Nishimune A, Henly JM. Emergng exracellular roles of protein SUMOylation in neuronal function and dysfunction. Nat Rev Neurosci 2007; 8(12): 948- 959. 10. Song J, Durrin LK, Wilkinson TA, Krontiris TG, Chen Y. Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc Natl Acad Sci 2004; 101: 14373-14378 11. Slow EF, Graham RF, Osmand AP ,Devon RS, Lu G, Deng Y, Pearson J, Vaid K, Bissada N, Wetzel R, Leavitt BR, Hayden MR, Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci USA 2005; 102: 11402–11407. 12. Krumova P, Weishaupt JH. Sumoylation in neurodegenerative diseases. Cell Mol Life Sci 2013; 70: 2123-2138. 13. Bowman AB, Yoo SY, Dantuma NP, Zoghbi HY. Neuronaldysfunction in a polyglutamine disease model occurs in the absence ofubiquitin– proteasome system impairment and inversely correlates withthe degree of nuclear inclusion formation. Hum Mol Genet 2005; 14: 679-691. 14. Steffan JS, Agrawal N, Pallos J, Rockabrand E, Trotman LC, Slepko N, Illes K, Lukacsovich T, Zhu Y-Z, Cattaneo E, Pandolfi P,Thompson LM, Marsh JL. SUMO modification of Huntingtin andHuntington’s disease pathology. Science 2004; 304: 100-104. 15. Subramaniam S, Sixt KM, Barrow R, Snyder SH. Rhes, a striatal specific protein, mediates mutant-huntingtincytotoxicity. Science 2009; 324: 1327-1330. 16. Terashima T, Kawai H, Fujitani M, Maeda K, Yasuda H. SUMO-1 co-localized with mutant atrophin-1 with expanded polyglutamines accelerates intranuclear aggregation and cell death. Neuroreport 2002; 13:2359-2364. 17. Neumann M, Müller V, Görner K, Kretzschmar HA, Haass C, Kahle PJ. Pathological properties of the Parkinson’s disease-associated protein DJ-1 in α-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol 2004; 107: 489-496. 18. Michels G, Hoppe UC. Rapid actions of and-rogens. Front Neuroendocrinol 2008; 29: 182-198. 19. Chan HY, Warrick JM, Andriola I, Merry D, Bonini NM. Geneticmodulation of polyglutamine toxicity by protein conjugation pathways inDrosophila. Hum Mol Genet 2002; 11: 2895-2904. 20. Mukherjee S, Thomas M, Dadgar N, Lieberman AP,Iiguez-Lluh JA. Small ubiquitin-like modifier(SUMO) modification of the androgen receptor attenuatespolyglutamine-mediated aggregation. J BiolChem 2009; 284: 21296- 21306. 21. Poukka H, Karvonen U, Janne OA, Palvimo JJ. Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci USA 2000; 97:14145-14150. 22. Chua JP, Reddy SL, Yu Z, Giorgetti E, Montie HL, Mukherjee S, Higgins J, McEachin RC, Robins DM,Merry DE, Iñiguez-Lluhí JA, Lieberman AP. Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease. J Clin Invest 2015; 2:831-845. 23. Ueda H, Goto J, Hashida H, Lin X, Oyanagi K, Kawano H, Zoghbi HY, Kanazawa I, Okazawa H. Enhanced SUMOylation in polyglutamine diseases. Biochem Biophys Res Commun 2002; 293: 307-313. 24. Ryu J, Cho S, Park BC, Lee Dh. Oxidative stressenhanced SUMOylation and aggregation of ataxin-1: implication of JNK pathway. Biochem Biophys Res Commun 2010; 393: 280-285. 25. Janer A, Werner A, Takahashi-Fujigasaki J, Daret A, Fujigasaki H, Takada K, Duyckaerts C, Brice A, Dejean A, Sittler A. SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7. Hum Mol Genet 2010; 19:181-195. 26. Lieberman AP, Robitaille Y, Trojanowski JQ, Dickson DW, Fischbeck KH. Polyglutamine-containing aggregates in neuronal intranuclear inclusion disease. Lancet 2010; 351:884 27. McFadden K, Hamilton RL, Insalaco SJ, Lavine L, Al-Mateen M, Wang G, Wiley CA. Neuronal intranuclear inclusion disease without polyglutamine inclusions in a child. J Neuropathol Exp Neurol 2005; 64:545–552 28. Takahashi-Fujigasaki J, Arai K, Funata N, Fujigasaki H. SUMOylation substrates in neuronal intranuclear inclusion disease. Neuropathol Appl Neurobiol 2006; 32:92–100 29. Sone J, Tanaka F, Koike H, Inukai A, Katsuno M, Yoshida M, Watanabe H, Sobue G. Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease. Neurology 2011; 76:1372–1376 30. Zhao X, Sternsdorf T, Bolger TA, Evans RM, Yao TP. Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Mol Cell Biol 2005; 25:8456–8464 31. Eckermann K. SUMO and Parkinson’s disease. Neuromolecular Med. 2013; 15(4):737-59. doi: 10.1007/s12017-013-8259-5 32. Guerra de Souza AC, Prediger RD, Cimarosti H. SUMO-regulated mitochondrial function in Parkinson’s disease. Journal of Neurochemistry 2016;137:673-686 33. Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 2005;123:383–396 34. Kunadt M, Eckermann K, Stuendl A, Gong J, Russo B, Strauss K, Rai S, Kügler S, Lockhart LF, Schwalbe M, Krumova P, Oliveira LMA, Bahr M, Mobius W, Levin J, Giese A, Kruse N, Mollenhauer B, Friedlander RG, Ludolph AC, Freischmidt A, Feiler MS, Danzer KM, Zweckstetter M, Jovin TM, Simons M, Weishaupt JH, Schneider A. Extracellular vesicle sorting of α-synuclein is regulated by SUMOylation. Acta Neuropathol 2015; 129: 695-713. 35. Krumova P, Weishaupt JH. Sumoylation in neurodegenerative diseases. Cell Mol Life Sci. 2013 Jun;70(12):2123-38. doi: 10.1007/ s00018-012-1158-3. Epub 2012 Sep 25. 36. Hoppe JB, Salbego CG, Cimarosti H. SUMOylation: Novel Neuroprotective Approach for Alzheimer’s Disease? Aging Dis. 2015; 1; 6(5): 322-30. 37. Lee L, Sakurai M, Matsuzaki S, Arancio O, Fraser P. SUMO and Alzheimer’s disease. Neuromolecular Med. 2013; 15(4): 720-736. 38. Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A, Jehu L, Segurado R, Stone D, Schadt E, Karnoub M, Nowotny P, Tacey K, Catanese J, Sninsky J, Brayne C, Rubinsztein D, Gill M, Lawlor B, Lovestone S, Holmans P, O’Donovan M, Morris JC, Thal L, Goate A, Owen MJ, Williams J. Evidence for novel susceptibility genes for late-onset Alzheimer’s disease from a genome-wide association study of putative functional variants. Hum Mol Genet 2007; 16(8): 865-873. 39. Weeraratna AT, Kalehua A, Deleon I, Bertak D, Maher G, Wade MS, Lustig A, Becker KG, Wood W, Walker DG, Beach TG, Taub DD. Alterations in immunological and neurological gene expression patterns in Alzheimer’s disease tissues. Exp Cell Res 2007; 1; 313(3):450-461. 40. Li Y, Wang H, Wang S, Quon D, Liu YW, Cordell B. Positive and negative regulation of APP amyloidogenesis by sumoylation. Proc Natl Acad Sci USA. 2003; 7; 100(1): 259-64. 41. Martins WC, Tasca CI, Cimarosti H.Battling Alzheimer’s Disease: Targeting SUMOylation- Mediated Pathways. Neurochem Res. 2016; 41(3): 568-578.

Nörodejeneratif Hastalıklar Ve SUMO

Yıl 2017, Cilt: 7 Sayı: 13, 59 - 70, 01.06.2017

Öz

Bu derlemede nörodejeneratif hastalıkların patofizyolojisinde önemi gittikçe daha da artan SUMO

(Small ubiquitin-like modifiers) proteinlerinin hastalıkların mekanizmasındaki işlevleri üzerinde durulacaktır.

SUMO proteinleri hücresel proseslerde önemli ölçüde rol oynamaktadır. SUMO ailesinden

(memelilerde dört farklı SUMO tanımlanmıştır: SUMO1, SUMO2, SUMO3, SUMO4) herhangi birinin hedef

proteinlerdeki lizin kalıntılarıyla oluşturdukları geri dönüşümlü kovalent bağlar sumolasyon işlemi

olarak bilinmektedir ve sumolasyon döngüsünde meydana gelen bozulmalar birçok nörolojik bozukluk

ile ilişkilendirilmiştir. Huntingtin, ataksin-1, tau ve α-sinükleinin SUMO substratları olarak tanımlanması

sumolasyon ve nörodejeneratif hastalıklar arasındaki ilişkiyi destekler yöndedir. Bu derleme kapsamında

ilk önce SUMO proteinleri ve sumolasyon hakkında bilgi verilecek daha sonra nörodejeneratif

hastalıklardan poliglutamin bozukluğuyla ilişkili hastalıkların, nöronal intranükleer inklüzyon hastalığının,

Parkinson hastalığının ve Alzheimer hastalığın SUMO proteinleri ile olan ilişkisine yönelik güncel

bilgiler aktarılacaktır.


Kaynakça

  • 1. Anderson DB, Zanella CA, Henley JM, Cimarotsi H. Sumoylation: Implications for Neurode-generative Diseases. Adv Exp Med Biol 2017; 963: 261-281. 2. Dorval V, Fraser PE. SUMO on the road to neurodegeneration. Biochim Biophys Acta 2007;1773: 694-706. 3. Li M, Guo D, Isales CM., Eizirik DL, Atkinson M, She JX, Wang CY. Sumo wrestling with type 1 diabetes. J Mol Med 2005; 83: 504- 513. 4. Wang CY, SHE JX. SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab Res Rev 2008; 24: 93–102. 5. Bohren KM, nadkarni V, Song JH, Gabbay KH,Owerbach, D. A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J Biol Chem 2004; 279: 27233–27238. 6. Rodriguez MS, Desterro JM, Lain S, Midgley CA, Lane DP, Hay RT. SUMO-1 modification activates the transcriptional response of p53. EMBO J 1999; 15: 6455-6461. 7. Tatham MH, Jaffray E, Vaughan OA, Desterro JMP, Botting CH, Naismith JH, Hay RT. Polymeric Chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/ SAE2 and Ubc9. J Bio Chem 2001; 276(38): 35368-35374. 8. Wilkinson KA, Henley JM. Mechanisms, regulation and consequences of protein SUMOylation Biochem J 2012; 428(2): 133-145. 9. Martin S, Wilkinson KA, Nishimune A, Henly JM. Emergng exracellular roles of protein SUMOylation in neuronal function and dysfunction. Nat Rev Neurosci 2007; 8(12): 948- 959. 10. Song J, Durrin LK, Wilkinson TA, Krontiris TG, Chen Y. Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc Natl Acad Sci 2004; 101: 14373-14378 11. Slow EF, Graham RF, Osmand AP ,Devon RS, Lu G, Deng Y, Pearson J, Vaid K, Bissada N, Wetzel R, Leavitt BR, Hayden MR, Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci USA 2005; 102: 11402–11407. 12. Krumova P, Weishaupt JH. Sumoylation in neurodegenerative diseases. Cell Mol Life Sci 2013; 70: 2123-2138. 13. Bowman AB, Yoo SY, Dantuma NP, Zoghbi HY. Neuronaldysfunction in a polyglutamine disease model occurs in the absence ofubiquitin– proteasome system impairment and inversely correlates withthe degree of nuclear inclusion formation. Hum Mol Genet 2005; 14: 679-691. 14. Steffan JS, Agrawal N, Pallos J, Rockabrand E, Trotman LC, Slepko N, Illes K, Lukacsovich T, Zhu Y-Z, Cattaneo E, Pandolfi P,Thompson LM, Marsh JL. SUMO modification of Huntingtin andHuntington’s disease pathology. Science 2004; 304: 100-104. 15. Subramaniam S, Sixt KM, Barrow R, Snyder SH. Rhes, a striatal specific protein, mediates mutant-huntingtincytotoxicity. Science 2009; 324: 1327-1330. 16. Terashima T, Kawai H, Fujitani M, Maeda K, Yasuda H. SUMO-1 co-localized with mutant atrophin-1 with expanded polyglutamines accelerates intranuclear aggregation and cell death. Neuroreport 2002; 13:2359-2364. 17. Neumann M, Müller V, Görner K, Kretzschmar HA, Haass C, Kahle PJ. Pathological properties of the Parkinson’s disease-associated protein DJ-1 in α-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol 2004; 107: 489-496. 18. Michels G, Hoppe UC. Rapid actions of and-rogens. Front Neuroendocrinol 2008; 29: 182-198. 19. Chan HY, Warrick JM, Andriola I, Merry D, Bonini NM. Geneticmodulation of polyglutamine toxicity by protein conjugation pathways inDrosophila. Hum Mol Genet 2002; 11: 2895-2904. 20. Mukherjee S, Thomas M, Dadgar N, Lieberman AP,Iiguez-Lluh JA. Small ubiquitin-like modifier(SUMO) modification of the androgen receptor attenuatespolyglutamine-mediated aggregation. J BiolChem 2009; 284: 21296- 21306. 21. Poukka H, Karvonen U, Janne OA, Palvimo JJ. Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci USA 2000; 97:14145-14150. 22. Chua JP, Reddy SL, Yu Z, Giorgetti E, Montie HL, Mukherjee S, Higgins J, McEachin RC, Robins DM,Merry DE, Iñiguez-Lluhí JA, Lieberman AP. Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease. J Clin Invest 2015; 2:831-845. 23. Ueda H, Goto J, Hashida H, Lin X, Oyanagi K, Kawano H, Zoghbi HY, Kanazawa I, Okazawa H. Enhanced SUMOylation in polyglutamine diseases. Biochem Biophys Res Commun 2002; 293: 307-313. 24. Ryu J, Cho S, Park BC, Lee Dh. Oxidative stressenhanced SUMOylation and aggregation of ataxin-1: implication of JNK pathway. Biochem Biophys Res Commun 2010; 393: 280-285. 25. Janer A, Werner A, Takahashi-Fujigasaki J, Daret A, Fujigasaki H, Takada K, Duyckaerts C, Brice A, Dejean A, Sittler A. SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7. Hum Mol Genet 2010; 19:181-195. 26. Lieberman AP, Robitaille Y, Trojanowski JQ, Dickson DW, Fischbeck KH. Polyglutamine-containing aggregates in neuronal intranuclear inclusion disease. Lancet 2010; 351:884 27. McFadden K, Hamilton RL, Insalaco SJ, Lavine L, Al-Mateen M, Wang G, Wiley CA. Neuronal intranuclear inclusion disease without polyglutamine inclusions in a child. J Neuropathol Exp Neurol 2005; 64:545–552 28. Takahashi-Fujigasaki J, Arai K, Funata N, Fujigasaki H. SUMOylation substrates in neuronal intranuclear inclusion disease. Neuropathol Appl Neurobiol 2006; 32:92–100 29. Sone J, Tanaka F, Koike H, Inukai A, Katsuno M, Yoshida M, Watanabe H, Sobue G. Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease. Neurology 2011; 76:1372–1376 30. Zhao X, Sternsdorf T, Bolger TA, Evans RM, Yao TP. Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Mol Cell Biol 2005; 25:8456–8464 31. Eckermann K. SUMO and Parkinson’s disease. Neuromolecular Med. 2013; 15(4):737-59. doi: 10.1007/s12017-013-8259-5 32. Guerra de Souza AC, Prediger RD, Cimarosti H. SUMO-regulated mitochondrial function in Parkinson’s disease. Journal of Neurochemistry 2016;137:673-686 33. Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 2005;123:383–396 34. Kunadt M, Eckermann K, Stuendl A, Gong J, Russo B, Strauss K, Rai S, Kügler S, Lockhart LF, Schwalbe M, Krumova P, Oliveira LMA, Bahr M, Mobius W, Levin J, Giese A, Kruse N, Mollenhauer B, Friedlander RG, Ludolph AC, Freischmidt A, Feiler MS, Danzer KM, Zweckstetter M, Jovin TM, Simons M, Weishaupt JH, Schneider A. Extracellular vesicle sorting of α-synuclein is regulated by SUMOylation. Acta Neuropathol 2015; 129: 695-713. 35. Krumova P, Weishaupt JH. Sumoylation in neurodegenerative diseases. Cell Mol Life Sci. 2013 Jun;70(12):2123-38. doi: 10.1007/ s00018-012-1158-3. Epub 2012 Sep 25. 36. Hoppe JB, Salbego CG, Cimarosti H. SUMOylation: Novel Neuroprotective Approach for Alzheimer’s Disease? Aging Dis. 2015; 1; 6(5): 322-30. 37. Lee L, Sakurai M, Matsuzaki S, Arancio O, Fraser P. SUMO and Alzheimer’s disease. Neuromolecular Med. 2013; 15(4): 720-736. 38. Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A, Jehu L, Segurado R, Stone D, Schadt E, Karnoub M, Nowotny P, Tacey K, Catanese J, Sninsky J, Brayne C, Rubinsztein D, Gill M, Lawlor B, Lovestone S, Holmans P, O’Donovan M, Morris JC, Thal L, Goate A, Owen MJ, Williams J. Evidence for novel susceptibility genes for late-onset Alzheimer’s disease from a genome-wide association study of putative functional variants. Hum Mol Genet 2007; 16(8): 865-873. 39. Weeraratna AT, Kalehua A, Deleon I, Bertak D, Maher G, Wade MS, Lustig A, Becker KG, Wood W, Walker DG, Beach TG, Taub DD. Alterations in immunological and neurological gene expression patterns in Alzheimer’s disease tissues. Exp Cell Res 2007; 1; 313(3):450-461. 40. Li Y, Wang H, Wang S, Quon D, Liu YW, Cordell B. Positive and negative regulation of APP amyloidogenesis by sumoylation. Proc Natl Acad Sci USA. 2003; 7; 100(1): 259-64. 41. Martins WC, Tasca CI, Cimarosti H.Battling Alzheimer’s Disease: Targeting SUMOylation- Mediated Pathways. Neurochem Res. 2016; 41(3): 568-578.
Toplam 1 adet kaynakça vardır.

Ayrıntılar

Bölüm Makale
Yazarlar

Ulaş Ay Bu kişi benim

Melis Şen Bu kişi benim

Ece Akbayır Bu kişi benim

Erdem Tüzün

Cem İsmail Küçükali

Yayımlanma Tarihi 1 Haziran 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 7 Sayı: 13

Kaynak Göster

APA Ay, U., Şen, M., Akbayır, E., Tüzün, E., vd. (2017). Nörodejeneratif Hastalıklar Ve SUMO. Deneysel Tıp Araştırma Enstitüsü Dergisi, 7(13), 59-70.
AMA Ay U, Şen M, Akbayır E, Tüzün E, Küçükali Cİ. Nörodejeneratif Hastalıklar Ve SUMO. Deneysel Tıp Araştırma Enstitüsü Dergisi. Haziran 2017;7(13):59-70.
Chicago Ay, Ulaş, Melis Şen, Ece Akbayır, Erdem Tüzün, ve Cem İsmail Küçükali. “Nörodejeneratif Hastalıklar Ve SUMO”. Deneysel Tıp Araştırma Enstitüsü Dergisi 7, sy. 13 (Haziran 2017): 59-70.
EndNote Ay U, Şen M, Akbayır E, Tüzün E, Küçükali Cİ (01 Haziran 2017) Nörodejeneratif Hastalıklar Ve SUMO. Deneysel Tıp Araştırma Enstitüsü Dergisi 7 13 59–70.
IEEE U. Ay, M. Şen, E. Akbayır, E. Tüzün, ve C. İ. Küçükali, “Nörodejeneratif Hastalıklar Ve SUMO”, Deneysel Tıp Araştırma Enstitüsü Dergisi, c. 7, sy. 13, ss. 59–70, 2017.
ISNAD Ay, Ulaş vd. “Nörodejeneratif Hastalıklar Ve SUMO”. Deneysel Tıp Araştırma Enstitüsü Dergisi 7/13 (Haziran 2017), 59-70.
JAMA Ay U, Şen M, Akbayır E, Tüzün E, Küçükali Cİ. Nörodejeneratif Hastalıklar Ve SUMO. Deneysel Tıp Araştırma Enstitüsü Dergisi. 2017;7:59–70.
MLA Ay, Ulaş vd. “Nörodejeneratif Hastalıklar Ve SUMO”. Deneysel Tıp Araştırma Enstitüsü Dergisi, c. 7, sy. 13, 2017, ss. 59-70.
Vancouver Ay U, Şen M, Akbayır E, Tüzün E, Küçükali Cİ. Nörodejeneratif Hastalıklar Ve SUMO. Deneysel Tıp Araştırma Enstitüsü Dergisi. 2017;7(13):59-70.