1887

Journal of General Virology header logo

Volume 95, Issue 7

Complex proteinopathy with accumulations of prion protein, hyperphosphorylated tau, α-synuclein and ubiquitin in experimental bovine spongiform encephalopathy of monkeys Free

Abstract

Proteins aggregate in several slowly progressive neurodegenerative diseases called ‘proteinopathies’. Studies with cell cultures and transgenic mice overexpressing mutated proteins suggested that aggregates of one protein induced misfolding and aggregation of other proteins as well – a possible common mechanism for some neurodegenerative diseases. However, most proteinopathies are ‘sporadic’, without gene mutation or overexpression. Thus, proteinopathies in WT animals genetically close to humans might be informative. Squirrel monkeys infected with the classical bovine spongiform encephalopathy agent developed an encephalopathy resembling variant Creutzfeldt–Jakob disease with accumulations not only of abnormal prion protein (PrP), but also three other proteins: hyperphosphorylated tau (p-tau), α-synuclein and ubiquitin; β-amyloid protein (Aβ) did not accumulate. Severity of brain lesions correlated with spongiform degeneration. No amyloid was detected. These results suggested that PrP enhanced formation of p-tau and aggregation of α-synuclein and ubiquitin, but not Aβ, providing a new experimental model for neurodegenerative diseases associated with complex proteinopathies.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.062083-0
2014-07-01
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/7/1612.html?itemId=/content/journal/jgv/10.1099/vir.0.062083-0&mimeType=html&fmt=ahah

References

  1. Balducci C., Forloni G. 2011; APP transgenic mice: their use and limitations. Neuromolecular Med 13:117–137 [View Article][PubMed]
     [Google Scholar]
  2. Ballatore C., Lee V. M. Y., Trojanowski J. Q. 2007; Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8:663–672 [View Article][PubMed]
     [Google Scholar]
  3. Bautista M. J., Gutiérrez J., Salguero F. J., Fernández de Marco M. M., Romero-Trevejo J. L., Gómez-Villamandos J. C. 2006; BSE infection in bovine PrP transgenic mice leads to hyperphosphorylation of tau-protein. Vet Microbiol 115:293–301 [View Article][PubMed]
     [Google Scholar]
  4. Bersano A., Fiorini M., Allaria S., Zanusso G., Fasoli E., Gelati M., Monaco H., Squintani G., Monaco S., Nobile-Orazio E. 2006; Detection of CSF 14-3-3 protein in Guillain–Barré syndrome. Neurology 67:2211–2216 [View Article][PubMed]
     [Google Scholar]
  5. Bu B., Klunemann H., Suzuki K., Li J., Bird T., Jin L. W., Vincent I. 2002; Niemann–Pick disease type C yields possible clue for why cerebellar neurons do not form neurofibrillary tangles. Neurobiol Dis 11:285–297 [View Article][PubMed]
     [Google Scholar]
  6. Ferrer I., Santpere G., van Leeuwen F. W. 2008; Argyrophilic grain disease. Brain 131:1416–1432 [View Article][PubMed]
     [Google Scholar]
  7. Fluharty B. R., Biasini E., Stravalaci M., Sclip A., Diomede L., Balducci C., La Vitola P., Messa M., Colombo L.other authors 2013; An N-terminal fragment of the prion protein binds to amyloid-β oligomers and inhibits their neurotoxicity in vivo . J Biol Chem 288:7857–7866 [View Article][PubMed]
     [Google Scholar]
  8. Forloni G., Sclip A., Borsello T., Balducci C. 2013; The neurodegeneration in Alzheimer disease and the prion protein. Prion 7:60–65 [View Article][PubMed]
     [Google Scholar]
  9. Fraser H., Dickinson A. G. 1967; Distribution of experimentally induced scrapie lesions in the brain. Nature 216:1310–1311 [View Article][PubMed]
     [Google Scholar]
  10. Furuoka H., Horiuchi M., Yamakawa Y., Sata T. 2011; Predominant involvement of the cerebellum in guinea pigs infected with bovine spongiform encephalopathy (BSE). J Comp Pathol 144:269–276 [View Article][PubMed]
     [Google Scholar]
  11. Ghetti B., Tagliavini F., Masters C. L., Beyreuther K., Giaccone G., Verga L., Farlow M. R., Conneally P. M., Dlouhy S. R.other authors 1989; Gerstmann–Sträussler–Scheinker disease. II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family. Neurology 39:1453–1461 [View Article][PubMed]
     [Google Scholar]
  12. Ghetti B., Piccardo P., Frangione B., Bugiani O., Giaccone G., Young K., Prelli F., Farlow M. R., Dlouhy S. R., Tagliavini F. 1996a; Prion protein amyloidosis. Brain Pathol 6:127–145 [View Article][PubMed]
     [Google Scholar]
  13. Ghetti B., Piccardo P., Spillantini M. G., Ichimiya Y., Porro M., Perini F., Kitamoto T., Tateishi J., Seiler C.other authors 1996b; Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. . Proc Natl Acad Sci U S A 93:744–748 [View Article][PubMed]
     [Google Scholar]
  14. Giaccone G., Mangieri M., Capobianco R., Limido L., Hauw J. J., Haïk S., Fociani P., Bugiani O., Tagliavini F. 2008; Tauopathy in human and experimental variant Creutzfeldt–Jakob disease. Neurobiol Aging 29:1864–1873 [View Article][PubMed]
     [Google Scholar]
  15. Giasson B. I., Forman M. S., Higuchi M., Golbe L. I., Graves C. L., Kotzbauer P. T., Trojanowski J. Q., Lee V. M. Y. 2003; Initiation and synergistic fibrillization of tau and α-synuclein. Science 300:636–640 [View Article][PubMed]
     [Google Scholar]
  16. Gilley J., Adalbert R., Coleman M. P. 2011; Modelling early responses to neurodegenerative mutations in mice. Biochem Soc Trans 39:933–938 [View Article][PubMed]
     [Google Scholar]
  17. Goodall C. A., Head M. W., Everington D., Ironside J. W., Knight R. S. G., Green A. J. E. 2006; Raised CSF phospho-tau concentrations in variant Creutzfeldt–Jakob disease: diagnostic and pathological implications. J Neurol Neurosurg Psychiatry 77:89–91 [View Article][PubMed]
     [Google Scholar]
  18. Green A. J. E., Andrews M. M., Bishop M. T., McKenzie J. M., McCord Y., Pennington C., Chohan G., Knight R. S. 2010; Elevated phosphorylated tau pT-181 in a possible PRNP codon 129 MV vCJD case. J Neurol Neurosurg Psychiatry 81:1408–1409 [View Article][PubMed]
     [Google Scholar]
  19. Hsich G., Kenney K., Gibbs C. J. Jr, Lee K. H., Harrington M. G. 1996; The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 335:924–930 [View Article][PubMed]
     [Google Scholar]
  20. Ince P. G., Clark B., Holton J., Revesz T., Wharton S. B. 2008; Diseases of movement and system degenerations. In Greenfield’s Neuropathology pp. 889–981 Edited by Seth L., Louis D. N., Ellison D. W. London: Hodder Arnold;
     [Google Scholar]
  21. Jayadev S., Nochlin D., Poorkaj P., Steinbart E. J., Mastrianni J. A., Montine T. J., Ghetti B., Schellenberg G. D., Bird T. D., Leverenz J. B. 2011; Familial prion disease with Alzheimer disease-like tau pathology and clinical phenotype. Ann Neurol 69:712–720 [View Article][PubMed]
     [Google Scholar]
  22. Jeffrey M., McGovern G., Chambers E. V., King D., González L., Manson J. C., Ghetti B., Piccardo P., Barron R. M. 2012; Mechanism of PrP-amyloid formation in mice without transmissible spongiform encephalopathy. Brain Pathol 22:58–66 [View Article][PubMed]
     [Google Scholar]
  23. Josephs K. A., Ahlskog J. E., Parisi J. E., Boeve B. F., Crum B. A., Giannini C., Petersen R. C. 2009; Rapidly progressive neurodegenerative dementias. Arch Neurol 66:201–207 [View Article][PubMed]
     [Google Scholar]
  24. Kirby L., Agarwal S., Graham J. F., Goldmann W., Gill A. C. 2010; Inverse correlation of thermal lability and conversion efficiency for five prion protein polymorphic variants. Biochemistry 49:1448–1459 [View Article][PubMed]
     [Google Scholar]
  25. Lasmézas C. I., Deslys J. P., Demaimay R., Adjou K. T., Lamoury F., Dormont D., Robain O., Ironside J., Hauw J. J. 1996; BSE transmission to macaques. Nature 381:743–744 [View Article][PubMed]
     [Google Scholar]
  26. Lasmézas C. I., Fournier J. G., Nouvel V., Boe H., Marcé D., Lamoury F., Kopp N., Hauw J. J., Ironside J.other authors 2001; Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt–Jakob disease: implications for human health. Proc Natl Acad Sci U S A 98:4142–4147 [View Article][PubMed]
     [Google Scholar]
  27. Lasmézas C. I., Comoy E., Hawkins S., Herzog C., Mouthon F., Konold T., Auvré F., Correia E., Lescoutra-Etchegaray N.other authors 2005; Risk of oral infection with bovine spongiform encephalopathy agent in primates. Lancet 365:781–783 [View Article][PubMed]
     [Google Scholar]
  28. Lowe J., Mirra S. S., Hyman B. T., Dickson D. W. 2008; Ageing and dementia. In Greenfield’s Neuropathology pp. 1031–1121 Edited by Seth L., Louis D. N., Ellison D. W. London: Hodder Arnold;
     [Google Scholar]
  29. Ludolph A. C., Kassubek J., Landwehrmeyer B. G., Mandelkow E., Mandelkow E. M., Burn D. J., Caparros-Lefebvre D., Frey K. A., de Yebenes J. G.other authors 2009; Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options. Eur J Neurol 16:297–309 [View Article][PubMed]
     [Google Scholar]
  30. Nath A., Sammalkorpi M., DeWitt D. C., Trexler A. J., Elbaum-Garfinkle S., O’Hern C. S., Rhoades E. 2012; The conformational ensembles of α-synuclein and tau: combining single-molecule FRET and simulations. Biophys J 103:1940–1949 [View Article][PubMed]
     [Google Scholar]
  31. Nygaard H. B., Strittmatter S. M. 2009; Cellular prion protein mediates the toxicity of beta-amyloid oligomers: implications for Alzheimer disease. Arch Neurol 66:1325–1328 [View Article][PubMed]
     [Google Scholar]
  32. Piccardo P., Cervenakova L., Vasilyeva I., Yakovleva O., Bacik I., Cervenak J., McKenzie C., Kurillova L., Gregori L.other authors 2011; Candidate cell substrates, vaccine production, and transmissible spongiform encephalopathies. Emerg Infect Dis 17:2262–2269 [View Article][PubMed]
     [Google Scholar]
  33. Piccardo P., Cervenak J., Cervenakova L., Yakovleva O., Vasilyeva I., McKenzie C., Gregori L., Pomeroy K., Seuberlich T., Asher D. M. 2012; Squirrel monkeys (Saimiri sciureus) infected with the agent of bovine spongiform encephalopathy develop tau pathology. J Comp Pathol 147:84–93 [View Article][PubMed]
     [Google Scholar]
  34. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [View Article][PubMed]
     [Google Scholar]
  35. Reiniger L., Lukic A., Linehan J., Rudge P., Collinge J., Mead S., Brandner S. 2011; Tau, prions and Aβ: the triad of neurodegeneration. Acta Neuropathol 121:5–20 [View Article][PubMed]
     [Google Scholar]
  36. Sepulveda-Falla D., Matschke J., Bernreuther C., Hagel C., Puig B., Villegas A., Garcia G., Zea J., Gomez-Mancilla B.other authors 2011; Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer’s disease. Brain Pathol 21:452–463 [View Article][PubMed]
     [Google Scholar]
  37. Shimizu S., Hoshi K., Muramoto T., Homma M., Ironside J. W., Kuzuhara S., Sato T., Yamamoto T., Kitamoto T. 1999; Creutzfeldt–Jakob disease with florid-type plaques after cadaveric dura mater grafting. Arch Neurol 56:357–362 [View Article][PubMed]
     [Google Scholar]
  38. Tagliavini F., Giaccone G., Prelli F., Verga L., Porro M., Trojanowski J. Q., Farlow M. R., Frangione B., Ghetti B., Bugiani O. 1993; A68 is a component of paired helical filaments of Gerstmann–Sträussler–Scheinker disease, Indiana kindred. Brain Res 616:325–329 [View Article][PubMed]
     [Google Scholar]
  39. Togo T., Sahara N., Yen S. H., Cookson N., Ishizawa T., Hutton M., de Silva R., Lees A., Dickson D. W. 2002; Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J Neuropathol Exp Neurol 61:547–556[PubMed]
     [Google Scholar]
  40. Tokutake T., Kasuga K., Yajima R., Sekine Y., Tezuka T., Nishizawa M., Ikeuchi T. 2012; Hyperphosphorylation of Tau induced by naturally secreted amyloid-β at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3β signaling pathway. J Biol Chem 287:35222–35233 [View Article][PubMed]
     [Google Scholar]
  41. Vlad C., Iurascu M. I., Slamnoiu S., Hengerer B., Przybylski M. 2012; Characterization of oligomerization-aggregation products of neurodegenerative target proteins by ion mobility mass spectrometry. Methods Mol Biol 896:399–412[PubMed]
     [Google Scholar]
  42. Walker L. C., Masters C., Beyreuther K., Price D. L. 1990; Amyloid in the brains of aged squirrel monkeys. Acta Neuropathol 80:381–387 [View Article][PubMed]
     [Google Scholar]
  43. Wang X. F., Dong C. F., Zhang J., Wan Y. Z., Li F., Huang Y. X., Han L., Shan B., Gao C.other authors 2008; Human tau protein forms complex with PrP and some GSS- and fCJD-related PrP mutants possess stronger binding activities with tau in vitro . Mol Cell Biochem 310:49–55 [View Article][PubMed]
     [Google Scholar]
  44. Wells G. A., Scott A. C., Johnson C. T., Gunning R. F., Hancock R. D., Jeffrey M., Dawson M., Bradley R. 1987; A novel progressive spongiform encephalopathy in cattle. Vet Rec 121:419–420 [View Article][PubMed]
     [Google Scholar]
  45. Will R. G., Ironside J. W., Zeidler M., Estibeiro K., Cousens S. N., Smith P. G., Alperovitch A., Poser S., Pocchiari M., Hofman A. 1996; A new variant of Creutzfeldt–Jakob disease in the UK. Lancet 347:921–925 [View Article][PubMed]
     [Google Scholar]
  46. Williams L., Brown P., Ironside J., Gibson S., Will R., Ritchie D., Kreil T. R., Abee C. 2007; Clinical, neuropathological and immunohistochemical features of sporadic and variant forms of Creutzfeldt–Jakob disease in the squirrel monkey (Saimiri sciureus). J Gen Virol 88:688–695 [View Article][PubMed]
     [Google Scholar]
  47. Wittmann C. W., Wszolek M. F., Shulman J. M., Salvaterra P. M., Lewis J., Hutton M., Feany M. B. 2001; Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293:711–714 [View Article][PubMed]
     [Google Scholar]
  48. Zanusso G., Fiorini M., Farinazzo A., Gelati M., Benedetti M. D., Ferrari S., Dalla Libera A., Capaldi S., Monaco H. L.other authors 2005; Phosphorylated 14-3-3zeta protein in the CSF of neuroleptic-treated patients. Neurology 64:1618–1620 [View Article][PubMed]
     [Google Scholar]
  49. Zanusso G., Fiorini M., Ferrari S., Gajofatto A., Cagnin A., Galassi A., Richelli S., Monaco S. 2011; Cerebrospinal fluid markers in sporadic Creutzfeldt–Jakob disease. Int J Mol Sci 12:6281–6292 [View Article][PubMed]
     [Google Scholar]
  50. Zhou M., Ottenberg G., Sferrazza G. F., Lasmézas C. I. 2012; Highly neurotoxic monomeric α-helical prion protein. Proc Natl Acad Sci U S A 109:3113–3118 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.062083-0
Loading
Complex proteinopathy with accumulations of prion protein, hyperphosphorylated tau, α-synuclein and ubiquitin in experimental bovine spongiform encephalopathy of monkeys
J. Gen. Virol. 95, 1612 (2014); https://doi.org/10.1099/vir.0.062083-0
/content/journal/jgv/10.1099/vir.0.062083-0
/content/journal/jgv/10.1099/vir.0.062083-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error