Encefalopatías espongiformes transmisibles.Bases moleculares, diagnóstico y perspectivas terapéuticas

  1. Vargas, A.M.
  2. Salto, R.
  3. Sola, M.M.
  4. Hortelano, P.
Revista:
Ars pharmaceutica

ISSN: 2340-9894,  0004-2927

Año de publicación: 2001

Volumen: 42

Número: 1-2

Páginas: 5-20

Tipo: Artículo

DIALNET GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Ars pharmaceutica

Resumen

Las encefalopatías espongiformes transmisibles constituyen un grupo de enfermedades neurodegenerativas que estánasociadas a la presencia en el tejido nervioso de agregados insolubles constituidos por una isoforma anómala de unaproteína denominada prión. Esta isoforma se produce por un cambio conformacional en una molécula que puedetransmitirse a otras proteínas priónicas normales. Las proteínas modificadas pierden su actividad biológica, desencadenándosela muerte de las neuronas por apoptosis. Los cambios conformacionales de los priones que derivan enenfermedad pueden deberse a la existencia de mutaciones que disminuyan la estabilidad de las formas celulares.Existe susceptibilidad genética, por tanto, a padecer tipos hereditarios de la enfermedad o adquiridos por infeccióncon isoformas priónicas anormales. En la actualidad se están perfeccionando métodos sensibles de diagnósticobasados en la detección de las isoformas anormales de la proteína priónica. Todavía no existen tratamientos curativospara estas enfermedades aunque se están diseñando métodos terapéuticos que bloqueen los cambios conformacionalesque conducen a la precipitación de la proteína priónica.

Referencias bibliográficas

  • Basler K., Oesch B., Scott M., Westaway D., Walchli M., Groth D. F., McKinley M. P., Prusiner S. B. and Weissmann C. (1986) Scrapie and Cellular PrP Isoforms Are Encoded by the Same Chromosomal Gene. Cell 46, 417-428.
  • Beaudry P., Cohen P., Brandel J. P., Delasnerielaupretre N., Richard S. Launay J. M. and Laplanche J. L. (1999) 14-3-3-Protein, Neuron-Specific Enolase, and S-100-Protein in Cerebrospinal-Fluid of Patients with Creutzfeldt-Jakob-Disease. Dement. Geriatr. Cogn. Dis. 10, 40-46.
  • Bieschke J., Giese A., Schulzschaeffer W., Zerr I., Poser S., Eigen M. and Kretzschmar H. (2000) Ultrasensitive Detection of Pathological Prion Protein Aggregates by Dual-Color Scanning for Intensely Fluorescent Targets. Proc. Natl. Acad. Sci. USA 97, 5468-5473.
  • Bodemer W. (1999) The Use of Monoclonal-Antibodies in Human Prion Disease. Naturwissenschaften 86, 212-220.
  • Brown D. R. (2001) Prion and prejudice: normal protein and the synapse Trends Neurosci. 24, 85-90.
  • Brown D. R., Wong B. S., Hafiz F., Clive C., Haswell S. J. and Jones I. M. (1999) Normal prion protein has an activity like that of superoxide dismutase. Biochem. J. 344, 1-5.
  • Caspi S., Halimi M., Yanai A., Sasson S. B., Taraboulos A. and Gabizon R. (1998) The anti-prion activity of Congo red. Putative mechanism. J. Biol. Chem. 273, 3484-3489.
  • Caughey B, Brown K., Raymond G. J., Katzenstein G. E. and Thresher W. (1994) Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and congo red. J. Virol. 68, 2135-2141.
  • Caughey B., Kocisko D.A., Raymond G.J. and Lansbury P. T. Jr. (1995) Aggregates of scrapie-associated prion protein induce the cell-free conversion of protease-sensitive prion protein to the protease-resistant state. Chem. Biol. 2, 807-817.
  • Cavallaro S., Gibbs C. J. and Pergami P. (1999) Early Induction of Protein Nexin-I in Scrapie. Neuroreport. 8, 1677-1681.
  • Endo T., Groth D., Prusiner S. B. and Kobata A. (1989) Diversity of oligosaccharide structures linked to asparagines of the scrapie prion protein. Biochemistry 28, 8380-8388.
  • Fischer M. B., Roeckl C., Parizek P., Schwarz H. P., and Aguzzi A (2000) Binding of disease-associated prion protein to plasminogen. Nature 23, 479-483.
  • Ingrosso L., Ladogana A. and Pocchiari M. (1995) Congo red prolongs the incubation period in scrapie-infected hamsters. J. Virol. 69, 506-508.
  • Ironside J. W. (1998) Neuropathological Findings in New Variant Cjd and Experimental Transmission of Bse. Fems Immunol. Med. Microbiol. 21, 91-95.
  • Kaneko K., Zulianello L., Scott M., Cooper C. M., Wallace A. C., James T. L., Cohen F. E. and Prusiner S. B. (1997) Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation. Proc. Natl. Acad. Sci. USA 94, 10069-10074.
  • Kascsak R. J., Fersko R., Pulgiano D., Rubenstein R. and Carp R. I. (1997) Immunodiagnosis of Prion Disease. Immunol. Invest. 26, 259-268.
  • Konaka K., Kaido M., Okuda Y., Aoike F., Abe K., Kitamoto T. and Yanagihara T. (2000) Proton Magnetic-Resonance Spectroscopy of a Patient with Gerstmann-Straussler-Scheinker-Disease. Neuroradiology 42, 662-665.
  • Kretzschmar H. A., Stowring L. E., Westaway D., Stubblebine W. H., Prusiner S. B. and Dearmond S. J. (1986) Molecular cloning of a human prion protein cDNA. DNA 5, 315-324.
  • Liu H., Farrjones S., Ulyanov N. B., Llinas M., Marqusee S., Groth D., Cohen F. E., Prusiner S. B. and James T. L. (1999) Solution Structure of Syrian-Hamster Prion Protein Rprp (90-231). Biochemistry 38, 5362-5377.
  • López-García F., Zahn R., Riek R. and Wuthrich K. (2000) NMR Structure of the Bovine Prion Protein. Proc. Natl. Acad. Sci. USA 97, 8334-8339.
  • Lugaresi E., Montagna P., Baruzzi A., Cortelli P., Tinuper P., Zucconi M., Gambetti P. L. and Medori R. (1986) Familial insomnia with a malignant course: a new thalamic disease. Rev. Neurol. (Paris) 142, 791-792.
  • Moore B. V. and Pérez V. J. (1967) Specific acidic proteins of the nervous system. In: Calson (ed.) Physiological and Biochemical Aspects of Nervous Integration. Prentice- Hall. pp. 343-359.
  • Morrissey M. P. and Shakhnovich E. I. (1999) Evidence for the Role of PrPC Helix-1 in the Hydrophilic Seeding of Prion Aggregates. Proc. Natl. Acad. Sci. USA 96, 11293-11298.
  • Muller W. E. G., Laplanche J. L., Ushijima H. and Schroder H. C. (2000) Novel Approaches in Diagnosis and Therapy of Creutzfeldt-Jakob-Disease. Mech. Ageing Dev. 116, 193-218.
  • Papakonstantinou E., Karakiulakis G., Roth M., Verghesenikolakaki S., Dawson M., Papadopoulos O. and Sklayiadis T. (1999) Glycosaminoglycan Analysis in Brain Stems from Animals Infected with the Bovine Spongiform Encephalopathy Agent. Arch. Biochem. Biophys. 370, 250-257.
  • Parchi P., Giese A., Capellari S., Brown P., Schulz-Schaeffer W., Windl O., Zerr I., Budka H., Kopp N. and Piccardo (1999) Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann. Neurol. 46, 224-233.
  • Perrier V., Wallace A. C., Kaneko K., Safar J., Prusiner S. B. And Cohen F. E. (2000) Mimicking dominant negative inhibition of prion replication through structure-based drug design. Proc. Natl. Acad. Sci. USA 97, 6073-6078.
  • Poser S., Mollenhauer B., Krauss A., Zerr I., Steinhoff B.J., Schroeter A., Finkenstaedt M., Schulzschaeffer W.J., Kretzschmar H.A. and Felgenhauer K. (1999) How to Improve the Clinical Diagnosis of Creutzfeldt Jakob Disease. Brain, 122, 2345-2351.
  • Priola S. A., Raines A. and Caughey W. S. (2000) Porphyrin and phthalocyanine antiscrapie compounds. Science 287, 1503-1506.
  • Prusiner S. B. (1982) Novel proteinaceous infectious particles cause scrapie. Science 216, 136-144.
  • Prusiner S.B. (1995) The Prion Diseases. Sci. Am. 272, 48-56.
  • Riek R., Wider G., Billeter M., Hornemann S., Glockshuber R. And Wüthrich K. (1998) Prion protein NMR structure and familial human spongiform encephalopathies. Proc Natl Acad Sci USA 95, 11667-11672.
  • Rittinger K., Budman J., Xu J. A., Volinia S., Cantley L. C., Smerdon S. J., Gamblin S. J. and Yaffe M. B. (1999) Structural-Analysis of 14-3-3 Phosphopeptide Complexes Identifies a Dual Role for the Nuclear Export Signal of 14-3-3 in Ligand-Binding. Mol. Cell 4, 153-166.
  • Rubenstein R., Gray P. C. Wehlburg C. M., Wagner J. S. and TisoneG. C. (1998) Detection and Discrimination of PrPSC by Multispectral Ultraviolet Fluorescence. Biochem. Biophys. Res. Commun. 246, 100-106.
  • Satoh J., Kurohara K., Yukitake M. and Kuroda Y. (1999) The 14-3-3-Protein Detectable in the Cerebrospinal-Fluid of Patients with Prion-Unrelated Neurological Diseases Is Expressed Constitutively in Neurons and Glial-Cells in Culture. Eur. Neurol., 41, 216-225.
  • Schaller O., Fatzer R., Stack M., Clark J., Cooley W., Biffiger K., Egli S., Doherr M., Vandevelde M., Heim D., Oesch B. and Moser M. (1999) Validation of a Western Immunoblotting Procedure for Bovine PrPSC Detection and Its Use as a Rapid Surveillance Method for the Diagnosis of Bovine Spongiform Encephalopathy (Bse). Acta Neuropathol. 98, 437-443.
  • Schlote W., Boellaard J. W., Schumm F. and Stöhr M. (1980) Gerstmann-Sträussler-Scheinker’s disease. Electron-microscopic observations on a brain biopsy. Acta Neuropathol. (Berl) 52, 203-211.
  • Stahl N., Baldwin M. A., Burlingame A. L. and Prusiner S. B. (1990) Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry 29, 8879-8884.
  • Tagliavini F., McArthur R. A., Canciani B., Giaccone G., Porro M., Bugiani M., Lievens P. M. J., Bugiani O., Peri E., Dall’Ara P., Rocchi M., Poli G., Forloni G., Bandiera T., Varasi M., Suarato A., Cassutti P., Cervini M. A., Lansen J., Salmona M. and Post C. (1997) Effectiveness of Anthracycline Against Experimental Prion Disease in Syrian Hamsters. Science 16, 1119-1121.
  • Thellung S., Florio T., Villa V., Corsaro A., Arena S., Amico C., Robello M., Salmona M., Forloni G., Bugiani O., Tagliavini F. and Schettini, G. (2000) Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in rat cerebellar granule cells treated with the prion protein fragment 106-126. J. Neurobiol. Dis. 7, 299-309.
  • Weber T., Otto M., Bodemer M. and Zerr I. (1997) Diagnosis of Creutzfeldt-Jakob-Disease and Related Human Spongiform Encephalopathies. Biomed. Pharmacother. 51, 381-387.
  • Yokoyama T. (1999) The Immunodetection of the Abnormal Isoform of Prion Protein. Histochem J. 31, 209-212.
  • Zahn R., Liu A. Z., Luhrs T., Riek R., Vonschroetter C., Garcia-Lopez F., Billeter M., Calzolai L., Wider G. and Wuthrich K. (2000) NMR Solution Structure of the Human Prion Protein. Proc. Natl. Acad. Sci. USA 97, 145-150.
  • Zulianello L., Kaneko K., Scott M., Erpel S., Han D., Cohen F. E. and Prusiner S. B. (2000) Dominant-negative inhibition of prion formation diminished by deletion mutagenesis of the prion protein. J. Virol. 74, 4351-4360.
Fuente de los datos: Dialnet