Abstract

Proteasomes are structures responsible for the elimination of damaged and misfolded proteins. Thus, they also regulate the most important intracellular processes. Changes in their functions can lead to many molecular diseases. There are two possible disorders in the function of proteasomes. Their increasing activity causes excessive degradation of important cell proteins. On the other hand, their insufficiency can inhibit the degradation of pathological proteins and lead to their accumulation.The increase of proteasome activity and the degradation of important proteins are observed in many pathological disorders. Therefore the study of pharmacological methods using proteasome inhibitors has gained growing interest in the last years. This review summarizes recent findings regarding the role of proteasomes in pathogenesis of selected diseases and discusses the potential use of proteasomes in diagnosis of different disorders.

References

• 1. Adams J.: The proteasome: structure, function and role in thecell. Cancer Treat. Rev., 2003; 29: 3-9
  Google Scholar
• 2. Almond J.B., Cohen G.M.: The proteasome: a novel target for cancerchemotherapy. Leukemia, 2002; 16: 433-443
  Google Scholar
• 3. Balasubramanyam M., Sampathkumar R., Mohan V.: Is insulinsignaling molecules misguided in diabetes for ubiquitin-proteasomemediated degradation. Mol. Cell. Biochem., 2005; 275: 117-125
  Google Scholar
• 4. Bubko I., Gruber B.M., Anuszewska E.L: Rola proteasomu w terapiichorób nieuleczalnych. Postepy Hig. Med. Dosw., 2010; 64: 314-325
  Google Scholar
• 5. Bury M., Niemierko A.: Proteasomalna degradacja białek komórkowych.Postępy Biol. Kom., 2005; 32: 435-448
  Google Scholar
• 6. Caldeira M.V., Salazar I.L., Curcio M., Canzoniero L.M., Duarte C.B.:Role of the ubiquitin-proteasome system in brain ischemia: friendor foe? Prog. Neurobiol., 2014; 112: 50-69
  Google Scholar
• 7. Calise J., Powell S.R.: The ubiquitin proteasome system and myocardialischemia. Am. J. Physiol. Heart Circ. Physiol, 2013; 304:H337-H349
  Google Scholar
• 8. Chai J., Wu Y., Sheng Z.: The relationship between skeletal muscleproteolysis and ubiquitin-proteasome proteolytic pathway inburned rats. Burns, 2002; 28: 527-533
  Google Scholar
• 9. Chang T.L., Chang. C.J., Lee W.J., Lin M.N., Huang Y.W., Fan K.: Theroles of ubiquitin and 26S proteasome in human obesity. Metabolism,2009; 58: 1643-1648
  Google Scholar
• 10. Edwards M.R., Bartlett N.W., Clarke D., Birrell M., Belvisi M.,Johnston S.L.: Targeting the NF-κB pathway in asthma and chronicobstructive pulmonary disease. Pharmacol. Ther., 2009; 121: 1-13
  Google Scholar
• 11. Elliott P.J., Pien C.S., McCormack T.A., Chapman I.D., Adams J.:Proteasome inhibition: a novel mechanism to combat asthma. J. AllergyClin. Immunol., 1999; 104: 294-300
  Google Scholar
• 12. Elliott P.J., Zollner T.M., Boehncke W.H.: Proteasome inhibition:a new anti-inflammatory strategy. J. Mol. Med., 2003; 81: 235-245
  Google Scholar
• 13. Gerrds W.L., de Jong W.W., Boelens W., Bloemendal H.: Structureand assembly of the 20S proteasome. Cell. Mol. Life Sci.,1998;54: 253-262
  Google Scholar
• 14. Golab J., Bauer T.M, Daniel V, Naujokat C.: Role of the ubiquitin-proteasome pathway in the diagnosis of human diseases. Clin.Chim. Acta, 2004; 340: 27-40
  Google Scholar
• 15. Hasselgren P.: Role of the ubiquitine-proteasome pathway insepsis-induced muscle catabolism. Mol. Biol. Rep., 1999; 26: 71-76
  Google Scholar
• 16. Hatakeyma S., Nakayama K.: Ubiquitylation as a quality controlsystem for intracellural proteins. J. Biochem., 2003; 134: 1-8
  Google Scholar
• 17. Herrmann J., Ciechanover A., Lerman L.O., Lerman A .: The ubiquitin-proteasome system in cardiovascular diseases – a hypothesisextended. Cardiovasc. Res., 2004; 61: 11-21
  Google Scholar
• 18. Hilker R., Brotchie J.M., Chapman J.: Pros and cons of a prion likepathogenesis in Parkinson’s disease. BMC Neurol., 2011; 11: 74-78
  Google Scholar
• 19. Huang L., Chen C.H.: Proteasomes regulators: activators andinhibitors. Curr. Med. Chem., 2009; 16: 931-939
  Google Scholar
• 20. Kazula A., Kazula E.: Proteasomy a nowe kierunki terapii. Farm.Pol., 2009; 65: 511-523
  Google Scholar
• 21. Lentsch A.B., Ward P.A.: Regulation of experimental lung inflammation.Respir. Physiol., 2001; 128: 17-22
  Google Scholar
• 22. Letoha T., Somlai C., Takacs T., Szabolcs A., Rakonczay Z. Jr., JármayK., Szalontai T., Varga I., Kaszaki J., Boros I., Duda E., Hackler L.,Kurucz I., Penke B.: The proteasome inhibitor MG132 protects againstacute pancreatitis. Free Radic. Biol. Med., 2005; 39: 1142-1151
  Google Scholar
• 23. Li X.J., Li S.: Proteasomal dysfunction in aging and Huntingtondisease. Neurobiol. Dis., 2011; 43: 4-8
  Google Scholar
• 24. Liu H., Pope R.M.: The role of apoptosis in rheumatoid arthritis.Curr. Opin. Pharmacol., 2003; 3: 317-322
  Google Scholar
• 25. Matuszczak E., Tylicka M., Dębek W., Hermanowicz A., OstrowskaH.: Correlation between circulating proteasome activity, totalprotein and C-reactive protein levels following burn in children.Burns, 2014; 40: 842-847
  Google Scholar
• 26. Michalak A., Krzeszowiak J., Markiewicz-Górka I.: Starzenie sięorganizmu a stres oksydacyjny oraz zmniejszona sprawność systemównaprawczych. Postepy Hig. Med. Dosw., 2014; 68: 1483-1491
  Google Scholar
• 27. Morawe T., Hiebel C., Kern A., Behl C.: Protein homeostasis, agingand Alzheimer’s disease. Mol. Neurobiol., 2012; 46: 41-54
  Google Scholar
• 28. Muddu A.K., Guha I.N., Elsharkawy A.M., Mann D.A.: Resolvingfibrosis in the diseased liver: translating the scientific promise tothe clinic. Int. J. Biochem. Cell Biol., 2007; 39: 695-714
  Google Scholar
• 29. Naujokat C., Hoffmann S.: Role and function of the 26S proteasomein proliferation and apoptosis. Lab. Invest., 2002; 82: 965-980
  Google Scholar
• 30. Orłowski M., Wilk S.: Ubiquitin-independent proteolytic functionsof the proteasome. Arch. Biochem. Biophys., 2003; 415: 1-5
  Google Scholar
• 31. Pereira C., Murphy K., Jeschke M., Herndon D.N.: Post burnmuscle wasting and the effects of treatments. Int. J. Biochem. CellBiol., 2005; 37: 1948-1961
  Google Scholar
• 32. Perez R.G., Hastings T.G.: Could a loss of α-synuclein function putdopaminergic neurons at risk?. J. Neurochem., 2004; 89: 1318-1324
  Google Scholar
• 33. Phillips J.B., Williams A.J., Adams J., Elliott P.J., Tortella F.C.:Proteasome inhibitor PS519 reduces infarction and attenuates leukocyteinfiltration in a rat model of focal cerebral ischemia. Stroke,2000; 31: 1686-1693
  Google Scholar
• 34. Qureshi N., Vogel S.N., Van Way C. 3rd, Papasian C.J., QureshiA.A., Morrison D.C.: The proteasome. A central regulator ofinflammation and macrophage function. Immunol. Res., 2005;31: 243-260
  Google Scholar
• 35. Rajan V., Mitch W.E.: Ubiquitin, proteasomes and proteolyticmechanism activated by kidney diseases. Biochim. Biophys. Acta,2008; 1782: 795-799
  Google Scholar
• 36. Roth G.A., Moser B., Krenn C., Roth-Walter F., Hetz H., RichterS., Brunner M., Jensen-Jarolim E., Wolner E., Hoetzenecker K.,Boltz-Nitulescu G., Ankersmit H.J.: Heightened levels of circulating20S proteasome in critically ill patients. Eur. J. Clin. Invest.,2005; 35: 399-403
  Google Scholar
• 37. Schmidt M., Finley D.: Regulation of proteasome activity in healthand disease. Biochim. Biophys. Acta, 2014; 1843: 13-25
  Google Scholar
• 38. Su V., Lau A.F.: Ubiquitin-like and ubiquitin-associated domainproteins: significance in proteasomal degradation. Cell. Mol. Life.Sci., 2009; 66: 2819-2833
  Google Scholar
• 39. Szwed A., Miłowska K.: Rola białek w chorobach neurodegeneracyjnych.Postepy Hig. Med. Dosw., 2012; 66: 187-195
  Google Scholar
• 40. Turnbull E.L., Rosser M.F., Cyr D.M.: The role of the UPS in cysticfibrosis. BMC Biochem., 2007; 8: S11
  Google Scholar
• 41. Tylicka M., Matuszczak E., Dębek W., Hermanowicz A., OstrowskaH.: Circulating proteasome activity following mild head injuryin children. Childs Nerv. Syst., 2014; 30: 1191-1196
  Google Scholar
• 42. Vankeerberghen A., Cuppens H., Cassiman J.: The cystic fibrosistransmembrane conductance regulator: an intriguing protein withpleiotropic functions. J. Cyst. Fibros., 2002; 1: 13-29
  Google Scholar
• 43. Visekruna A., Slavova N., Dullat S., Gröne J., Kroesen A.J., RitzJ.P., Buhr H.J., Steinhoff U.: Expression of catalytic proteasome subunitsin the gut of patients with Crohn’s disease. Int. J. Colorectal Dis.,2009; 24: 1133-1139
  Google Scholar
• 44. Wójcik C.: Proteasomy i szlak degradacji białek zależny od ubikwityny.Postępy Biol. Kom., 1995; 22: 295-315
  Google Scholar

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