Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector27810.17816/psaic278ReviewsОбзорыUnknownCreutzfeldt-Jakob disease: current issues (review)Болезнь Крейтцфельдта-Якоба: современные аспекты проблемы (обзор литературы)PeresedovaA. V.ПереседоваA. В.
Russian Federation
platonova@neurology.ruZavalishinI. A.ЗавалишинИ. A.
Russian Federation
platonova@neurology.ruResearch Center of Neurology, Russian Academy of Medical SciencesФГБУ «Научный центр неврологии» РАМН1003201261576302022017Copyright ©; 2012, Peresedova A.V., Zavalishin I.A.Copyright ©; 2012, Peresedova A.V., Zavalishin I.A.2012Peresedova A.V., Zavalishin I.A.Peresedova A.V., Zavalishin I.A.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/278

Creutzfeldt-Jakob disease and others human prion diseases are fatal neurodegenerative conditions. Etiologic classification includes sporadic, hereditary and acquired forms. Conformational change of the normal (cellular) form of prion protein (PrPc) to a pathological form (PrPSс) is considered central to formation of the infectious agent. In this article the molecular classification of sporadic CJD, the phenotypic variability and the major pathogenetic pathways in prion diseases have been analyzed. The unique resistance of prions to classic methods of decontamination, and evidence that prion diseases can be transmitted iatrogenically pose a serious control to decontamination procedures. Many therapeutic strategies have been tested as potential treatments for prion diseases in cell cultures and in animals. But only few trials of human prion disease have been published or ongoing.

Болезнь Крейтцфельдта-Якоба (БКЯ) относится к прионным болезням человека – группе фатальных нейродегенеративных заболеваний. Согласно этиологической классификации выделяют спорадические (идиопатические), приобретенные и наследственные формы. Возбудителем прионных болезней является инфекционный прионный белок (PrPSc), образующийся в результате конформационных изменений нормального (неинфекционного) клеточного белка PrPC. В статье освещены вопросы молекулярной классификации спорадической БКЯ, фенотипической вариабельности, приведены основные патогенетические механизмы при прионных заболеваниях. Уникальная резистентность прионов к классическим методам обеззараживания и возможность ятрогенной трансмиссии определяет необходимость строгого контроля за соблюдением процедур обеззараживания. В экспериментальных условиях (культура клеток и экспериментальные животные) разрабатываются различные терапевтические подходы при прионных заболеваниях, однако в клинической практике проведены или проводятся лишь несколько исследований.

Creutzfeldt-Jakob diseaseprionболезнь Крейтцфельдта-ЯкобаприонЗуев В.А., Завалишин И.А., Ройхель В.М. Прионные болезни человека и животных. Руководство для врачей. М.: Медицина, 1999; 192.Adori C., Kovacs G.G., Low P. et al. The ubiquitin-proteasome system in Creutzfeldt-Jakob and Alzheimer disease: intracellular redistribution of components correlates with neuronal vulnerability. Neurobiol. Dis. 2005; 19 (3): 427–435.Bade S., Frey A. Vaccines against transmissible spongiform encephalopathies: An urgent need? Human Vaccines 2008; 4 (1): 79–81.Beekes M. Variant Creutzfeldt-Jakob disease (vCJD): epidemiology and prevention from human to human secondary transmission. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2010; 53 (6): 597–605.Beekes M., McBride P.A. The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. FEBS J. 2007; 274 (3): 588–605.Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition, 2009 www.cdc.gov/biosafety/publications/bmbl5Collinge G., Gorham M., Hudson F. et al. Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial. Lancet Neurol. 2009; 8 (4): 334–344.Dorsey K., Zou S., Schonberger L.B. et al. Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in US surveillance study. Transfusion. 2009; 49 (5): 977–984.Everington D., Smith A.J., Ward H.J. et al. Dental treatment and risk of variant CJD – a case control study. Br. Dent. J. 2007; 202 (8): E19.Fournier J.G., Escaig-Haye F., Grigoriev V. Ultrastructural localization of prion proteins: physiological and pathological implications. Microsc. Res. Tech. 2000; 50(1): 76–88.Gambetti P., Dong Z., Yuan J. et al. A novel human disease with abnormal prion protein sensitive to protease. Ann. Neurol. 2008; 63 (6): 697–708.Gambetti P., Kong Q., Zou W. et al. Sporadic and familial CJD: classification and characterisation. Br. Med. Bull. 2003; 66: 213–239.Geschwind M.D. Clinical trials for prion disease: difficult challenges, but hope for the future. Lancet Neurol. 2009; 8 (4): 304–306.Glatzel M., Abela E., Maissen M., Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N. Engl. J. Med. 2003; 349 (19): 1812–1820.Hervé R., Secker T.J., Keevil C.W. Current risk of iatrogenic Creutzfeld-Jakob disease in the UK: efficacy of available cleaning chemistries and reusability of neurosurgical instruments. J. Hosp. Infect. 2010; 75 (4): 309–313.Klein M.A., Frigg R., Flechsig E. et al. A crucial role for B cells in neuroinvasive scrapie. Nature 1997; 390 (6661): 687–690.Kovacs G.G., Budka H. Molecular pathology of human prion diseases. Int. J. Mol. Sci. 2009; 10: 976–999.Kovacs G.G., Budka H. Prion diseases: from protein to cell pathology. Am. J. Pathol. 2008; 172 (3): 555–565.Kovacs G.G., Gelpi E., Ströbel T. et al. Involvement of the endosomal- lysosomal system correlates with regional pathology in Creutzfeldt-Jakob disease. J. Neuropathol. Exp. Neurol. 2007; 66 (7): 628–636.Kovacs G.G., Head M.W., Hegyi I. et al. Immunohistochemistry for the prion protein: comparison of different monoclonal antibodies in human prion disease subtypes.Brain Pathol. 2002; 12 (1): 1–11.Kovacs G.G., Kurucz I., Budka H. et al. Prominent stress response of Purkinje cells in Creutzfeldt-Jakob disease. Neurobiol. Dis. 2001; 8 (5): 881–889.Kovacs G.G., Preusser M., Strohschneider M., Budka H. Subcellular localization of disease-associated prion protein in the human brain. Am. J. Pathol. 2005; 166 (1): 287–294.Kunzi V., Glatzel M., Nakano M.Y. et al. Unhampered prion neuroinvasion despite impaired fast axonal transport in transgenic mice overexpressing four-repeat tau. J. Neurosci. 2002; 22 (17): 7471–7477.Ladogana A., Puopolo M., Croes E.A. et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia and Canada. Neurology. 2005; 64 (90): 1586–1591.Lawson V.A., Stewart J.D., Masters C.L. Enzymatic detergent treatment protocol that reduces protease-resistant prion protein load and infectivity from surgical-steel monofilaments contaminated with a human-derived prion strain. J. Gen. Virol. 2007; 88 (Pt 10): 2905–2914.Lehmann S., Pastore M., Rodez-Kreuz C. et al. New hospital disinfection processes for both conventional and prion infectious agents compatible with thermosensitive medical equipment. J. Hosp. Infect. 2009; 72 (4): 342–350.Liberski P.P., Sikorska B., Bratosiewicz-Wasik J. et al. Neuronal cell death in transmissible spongiform encephalopathies (prion diseases) revisited: from apoptosis to autophagy. Int. J. Biochem. Cell Biol. 2004; 36 (12): 2473–2490.Ludewigs H., Zuber C., Vana K. Therapeutic approaches for prion disorders. Expert Rev. Anti. Infect. Ther. 2007; 5 (4): 613–630.Lumley J.S., CJD Incidents Panel, Engineering and Scientific Advisory Committee-Pr., National Blood Transfusion Committee; Serious Hazards of Transfusion Committee. The impact of Creutzfeldt- Jakob disease on surgical practice. Ann. R. Coll Surg. Engl. 2008; 90 (2): 91–94.Manuelidis L., Yu Z.X., Barquero N., Mullins B. Cells infected with scrapie and Creutzfeldt-Jakob disease agents produce intracellular 25- nm virus-like particles. Proc. Natl. Acad. Sci. USA. 2007; 104: 1965–1970.Montrasio F., Frigg R., Glatzel M. et al. Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science 2000; 288 (5469): 1257–1259.Murray K., Peters J., Stellitano L. et al. Is there evidence of vertical transmission of variant Creutzfeldt-Jakob disease? J. Neurol. Neurosurg. Psychiatry 2011; 82 (7): 729–731.Notari S., Moleres F.J., Hunter S.B. et al. Multiorgan detection and characterization of protease-resistant prion protein in a case of variant CJD examined in the United States. PLoS One. 2010; 5 (1): e8765.Otto M., Cepek L., Ratzka P. et al. Efficacy of flupirtine on cognitive function in patients with CJD: A double-blind study. Neurology 2004; 62 (5): 714–718.Parchi P., Giese A. Phenotypic variability of sporadic human prion disease and its molecular basis: past, present, and future. Acta Neuropathol. 2011; 121: 91–112.Parchi P., Giese A., Capellari S. et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann. Neurol. 1999; 46 (20): 224–233.Peden A.H., Ironside J.W. Review: pathology of variant Creutzfeldt- Jakob disease. Folia Neuropathol. 2004; 42 Suppl. A: 85–91.Peden A.H., Ritchie D.L., Head M.W., Ironside J.W. Detection and localization of PrPSc in the skeletal muscle of patients with variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease.Am. J. Pathol. 2006; 168 (3): 927–935.Peden A.H., Ritchie D.L., Uddin H.P. et al. Abnormal prion protein in the pituitary in sporadic and variant Creutzfeldt-Jakob disease. J. Gen Virol. 2007; 88 (Pt 3): 1068-1072.Peretz D., Suppattapone S., Giles K. et al. Inactivation of prions by acidic sodium dodecyl sulfate. J. Virol. 2006; 80 (1): 322–331.Ponte M.L. Insights into the management of emerging infections: regulating variant Creutzfeldt-Jakob disease transfusion risk in the UK and the US. PLoS Med. 2006; 3 (10): e342.Prusiner S.B. Prions. Proc. Natl. Acad. Sci. USA. 1998; 95 (23): 13363–13383.Puopolo M., Ladogana A., Vetrugno V., Pacchiari M. Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases. Transfusion. 2011; 51 (7): 1556–1566.Relaño-Ginés A., Gabelle A., Lehmann S. et al. Gene and cell therapy for prion diseases. Infect. Disord. Drug Targets. 2009; 9 (1): 58–68. 63Rogez-Kreuz C., Yousfi R., Soufflet C. et al. Inactivation of animal and human prions by hydrogen peroxide gas plasma sterilization. Infect. Control. Hosp. Epidemiol. 2009; 30 (8): 769–777.Safar J., Wille H., Itri V. et al. Eight prion strains have PrP(Sc) molecules with different conformations. Nat. Med. 1998; 4 (10): 1157–1165.Sanchez-Juan P., Bishop M.T., Croes E.A. et al. A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease. BMC Med. Genet. 2011; 12: 73.Sanchez-Juan P., Cousens S.N., Will R.G., van Duijn C.M. Source of variant Creutzfeldt-Jakob disease outside United Kingdom. Emerg. Infect. Dis. 2007; 13 (8): 1166–1169.Spencer M.D., Knight R.S., Will R.G. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features. BMJ. 2002; 324 (7352): 1479–1482.Trevitt C.R., Collinge J. A systematic review of prion therapeutics in experimental models. Brain 2006; 129 (Pt 9): 2241–2265.Ward H.J., Everington D., Cousens S.N. et al. Risk factors for variant Creutzfeldt-Jakob disease: a case-control study. Ann. Neurol. 2006; 59 (1): 111–120.Westergard L., Christensen H.M., Harris D.A. The cellular prion protein (PrP(C)): its physiological function and role in disease. Biochim. Biophys. Acta. 2007; 1772 (6): 629–644.White M.D., Mallucci G.R. Therapy for prion diseases. Insights from the use of RNA interference. Prion 2009; 3 (3): 121–128.WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies. Report of a WHO consultation Geneva, Switzerland, 23–26 March 1999. www.who.int/csr/resources/publications/ bse/whocdscsraph2003.pdfWill R.G. Acquired prion disease: iatrogenic CJD, variant CJD, kuru. Br. Med. Bull. 2003; 66: 255–265.Yuan J., Xiao X., McGeehan J. et al. Insoluble aggregates and protease- resistant conformers of prion protein in uninfected human brains. J. Biol. Chem. 2006; 281 (460: 34848–3488.