This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Doh-ura, K.
Right arrow Articles by Caughey, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Doh-ura, K.
Right arrow Articles by Caughey, B.

 Previous Article  |  Next Article 

Journal of Virology, May 2000, p. 4894-4897, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Lysosomotropic Agents and Cysteine Protease Inhibitors Inhibit Scrapie-Associated Prion Protein Accumulation

Katsumi Doh-ura,1,* Toru Iwaki,1 and Byron Caughey2

Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan,1 and Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 598402

Received 13 December 1999/Accepted 15 February 2000

We report that lysosomotropic agents and cysteine protease inhibitors inhibited protease-resistant prion protein accumulation in scrapie-infected neuroblastoma cells. The inhibition occurred without either apparent effects on normal prion protein biosynthesis or turnover or direct interactions with prion protein molecules. The findings introduce two new classes of inhibitors of the formation of protease-resistant prion protein.

* Corresponding author. Mailing address: Department of Neuropathology, Neurological Institute, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-5537. Fax: 81-92-642-5540. E-mail: doh-ura{at}np.med.kyushu-u.ac.jp.

Journal of Virology, May 2000, p. 4894-4897, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hosokawa-Muto, J., Kamatari, Y. O., Nakamura, H. K., Kuwata, K. (2009). Variety of Antiprion Compounds Discovered through an In Silico Screen Based on Cellular-Form Prion Protein Structure: Correlation between Antiprion Activity and Binding Affinity. Antimicrob. Agents Chemother. 53: 765-771 [Abstract] [Full Text]  
  • Taguchi, Y., Shi, Z.-D., Ruddy, B., Dorward, D. W., Greene, L., Baron, G. S. (2009). Specific Biarsenical Labeling of Cell Surface Proteins Allows Fluorescent- and Biotin-tagging of Amyloid Precursor Protein and Prion Proteins. Mol. Biol. Cell 20: 233-244 [Abstract] [Full Text]  
  • Spilman, P., Lessard, P., Sattavat, M., Bush, C., Tousseyn, T., Huang, E. J., Giles, K., Golde, T., Das, P., Fauq, A., Prusiner, S. B., DeArmond, S. J. (2008). A {gamma}-secretase inhibitor and quinacrine reduce prions and prevent dendritic degeneration in murine brains. Proc. Natl. Acad. Sci. USA 105: 10595-10600 [Abstract] [Full Text]  
  • Kovacs, G. G., Budka, H. (2008). Prion Diseases: From Protein to Cell Pathology. Am. J. Pathol. 172: 555-565 [Abstract] [Full Text]  
  • Kawasaki, Y., Kawagoe, K., Chen, C.-j., Teruya, K., Sakasegawa, Y., Doh-ura, K. (2007). Orally Administered Amyloidophilic Compound Is Effective in Prolonging the Incubation Periods of Animals Cerebrally Infected with Prion Diseases in a Prion Strain-Dependent Manner. J. Virol. 81: 12889-12898 [Abstract] [Full Text]  
  • Webb, S., Lekishvili, T., Loeschner, C., Sellarajah, S., Prelli, F., Wisniewski, T., Gilbert, I. H., Brown, D. R. (2007). Mechanistic Insights into the Cure of Prion Disease by Novel Antiprion Compounds. J. Virol. 81: 10729-10741 [Abstract] [Full Text]  
  • Dirikoc, S., Priola, S. A., Marella, M., Zsurger, N., Chabry, J. (2007). Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity. J. Neurosci. 27: 9537-9544 [Abstract] [Full Text]  
  • Kuwata, K., Nishida, N., Matsumoto, T., Kamatari, Y. O., Hosokawa-Muto, J., Kodama, K., Nakamura, H. K., Kimura, K., Kawasaki, M., Takakura, Y., Shirabe, S., Takata, J., Kataoka, Y., Katamine, S. (2007). Hot spots in prion protein for pathogenic conversion. Proc. Natl. Acad. Sci. USA 104: 11921-11926 [Abstract] [Full Text]  
  • Doh-ura, K., Kuge, T., Uomoto, M., Nishizawa, K., Kawasaki, Y., Iha, M. (2007). Prophylactic Effect of Dietary Seaweed Fucoidan against Enteral Prion Infection. Antimicrob. Agents Chemother. 51: 2274-2277 [Abstract] [Full Text]  
  • Phuan, P.-W., Zorn, J. A., Safar, J., Giles, K., Prusiner, S. B., Cohen, F. E., May, B. C. H. (2007). Discriminating between cellular and misfolded prion protein by using affinity to 9-aminoacridine compounds. J. Gen. Virol. 88: 1392-1401 [Abstract] [Full Text]  
  • Zhu, J.-h., Horbinski, C., Guo, F., Watkins, S., Uchiyama, Y., Chu, C. T. (2007). Regulation of Autophagy by Extracellular Signal-Regulated Protein Kinases During 1-Methyl-4-Phenylpyridinium-Induced Cell Death. Am. J. Pathol. 170: 75-86 [Abstract] [Full Text]  
  • Farooqui, A. A., Ong, W.-Y., Horrocks, L. A. (2006). Inhibitors of Brain Phospholipase A2 Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders. Pharmacol. Rev. 58: 591-620 [Abstract] [Full Text]  
  • Trevitt, C. R, Collinge, J. (2006). A systematic review of prion therapeutics in experimental models. Brain 129: 2241-2265 [Abstract] [Full Text]  
  • Huang, Y., Okochi, H., May, B. C. H., Legname, G., Prusiner, S. B., Benet, L. Z., Guglielmo, B. J., Lin, E. T. (2006). QUINACRINE IS MAINLY METABOLIZED TO MONO-DESETHYL QUINACRINE BY CYP3A4/5 AND ITS BRAIN ACCUMULATION IS LIMITED BY P-GLYCOPROTEIN. Drug Metab. Dispos. 34: 1136-1144 [Abstract] [Full Text]  
  • May, B. C.H., Govaerts, C., Cohen, F. E. (2006). Developing therapeutics for the diseases of protein misfolding. Neurology 66: S118-S122 [Abstract] [Full Text]  
  • Kocisko, D. A., Caughey, B. (2006). Mefloquine, an Antimalaria Drug with Antiprion Activity In Vitro, Lacks Activity In Vivo. J. Virol. 80: 1044-1046 [Abstract] [Full Text]  
  • Bertsch, U., Winklhofer, K. F., Hirschberger, T., Bieschke, J., Weber, P., Hartl, F. U., Tavan, P., Tatzelt, J., Kretzschmar, H. A., Giese, A. (2005). Systematic Identification of Antiprion Drugs by High-Throughput Screening Based on Scanning for Intensely Fluorescent Targets. J. Virol. 79: 7785-7791 [Abstract] [Full Text]  
  • Novakofski, J., Brewer, M. S., Mateus-Pinilla, N., Killefer, J., McCusker, R. H. (2005). Prion biology relevant to bovine spongiform encephalopathy. J ANIM SCI 83: 1455-1476 [Abstract] [Full Text]  
  • Taniguchi, S., Suzuki, N., Masuda, M., Hisanaga, S.-i., Iwatsubo, T., Goedert, M., Hasegawa, M. (2005). Inhibition of Heparin-induced Tau Filament Formation by Phenothiazines, Polyphenols, and Porphyrins. J. Biol. Chem. 280: 7614-7623 [Abstract] [Full Text]  
  • Sandberg, M. K., Low, P. (2005). Altered Interaction and Expression of Proteins Involved in Neurosecretion in Scrapie-infected GT1-1 Cells. J. Biol. Chem. 280: 1264-1271 [Abstract] [Full Text]  
  • Haik, S., Brandel, J. P., Salomon, D., Sazdovitch, V., Delasnerie-Laupretre, N., Laplanche, J. L., Faucheux, B. A., Soubrie, C., Boher, E., Belorgey, C., Hauw, J. J., Alperovitch, A. (2004). Compassionate use of quinacrine in Creutzfeldt-Jakob disease fails to show significant effects. Neurology 63: 2413-2415 [Abstract] [Full Text]  
  • Kikuchi, Y., Kakeya, T., Sakai, A., Takatori, K., Nakamura, N., Matsuda, H., Yamazaki, T., Tanamoto, K.-i., Sawada, J.-i. (2004). Propagation of a protease-resistant form of prion protein in long-term cultured human glioblastoma cell line T98G. J. Gen. Virol. 85: 3449-3457 [Abstract] [Full Text]  
  • Kim, C.-L., Karino, A., Ishiguro, N., Shinagawa, M., Sato, M., Horiuchi, M. (2004). Cell-surface retention of PrPC by anti-PrP antibody prevents protease-resistant PrP formation. J. Gen. Virol. 85: 3473-3482 [Abstract] [Full Text]  
  • Ertmer, A., Gilch, S., Yun, S.-W., Flechsig, E., Klebl, B., Stein-Gerlach, M., Klein, M. A., Schatzl, H. M. (2004). The Tyrosine Kinase Inhibitor STI571 Induces Cellular Clearance of PrPSc in Prion-infected Cells. J. Biol. Chem. 279: 41918-41927 [Abstract] [Full Text]  
  • Kocisko, D. A., Morrey, J. D., Race, R. E., Chen, J., Caughey, B. (2004). Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice. J. Gen. Virol. 85: 2479-2483 [Abstract] [Full Text]  
  • Yadavalli, R., Guttmann, R. P., Seward, T., Centers, A. P., Williamson, R. A., Telling, G. C. (2004). Calpain-dependent Endoproteolytic Cleavage of PrPSc Modulates Scrapie Prion Propagation. J. Biol. Chem. 279: 21948-21956 [Abstract] [Full Text]  
  • Doh-ura, K., Ishikawa, K., Murakami-Kubo, I., Sasaki, K., Mohri, S., Race, R., Iwaki, T. (2004). Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models. J. Virol. 78: 4999-5006 [Abstract] [Full Text]  
  • Luhr, K. M., Nordstrom, E. K., Low, P., Ljunggren, H.-G., Taraboulos, A., Kristensson, K. (2004). Scrapie Protein Degradation by Cysteine Proteases in CD11c+ Dendritic Cells and GT1-1 Neuronal Cells. J. Virol. 78: 4776-4782 [Abstract] [Full Text]  
  • Murakami-Kubo, I., Doh-ura, K., Ishikawa, K., Kawatake, S., Sasaki, K., Kira, J.-i., Ohta, S., Iwaki, T. (2004). Quinoline Derivatives Are Therapeutic Candidates for Transmissible Spongiform Encephalopathies. J. Virol. 78: 1281-1288 [Abstract] [Full Text]  
  • Kocisko, D. A., Baron, G. S., Rubenstein, R., Chen, J., Kuizon, S., Caughey, B. (2003). New Inhibitors of Scrapie-Associated Prion Protein Formation in a Library of 2,000 Drugs and Natural Products. J. Virol. 77: 10288-10294 [Abstract] [Full Text]  
  • Zhang, Y., Spiess, E., Groschup, M. H., Burkle, A. (2003). Up-regulation of cathepsin B and cathepsin L activities in scrapie-infected mouse Neuro2a cells. J. Gen. Virol. 84: 2279-2283 [Abstract] [Full Text]  
  • Barret, A., Tagliavini, F., Forloni, G., Bate, C., Salmona, M., Colombo, L., De Luigi, A., Limido, L., Suardi, S., Rossi, G., Auvre, F., Adjou, K. T., Sales, N., Williams, A., Lasmezas, C., Deslys, J. P. (2003). Evaluation of Quinacrine Treatment for Prion Diseases. J. Virol. 77: 8462-8469 [Abstract] [Full Text]  
  • Daude, N., Marella, M., Chabry, J. (2003). Specific inhibition of pathological prion protein accumulation by small interfering RNAs. J. Cell Sci. 116: 2775-2779 [Abstract] [Full Text]  
  • Caughey, B. (2003). Prion protein conversions: insight into mechanisms, TSE transmission barriers and strains. Br Med Bull 66: 109-120 [Abstract] [Full Text]  
  • Kirby, L., Birkett, C. R., Rudyk, H., Gilbert, I. H., Hope, J. (2003). In vitro cell-free conversion of bacterial recombinant PrP to PrPres as a model for conversion. J. Gen. Virol. 84: 1013-1020 [Abstract] [Full Text]  
  • May, B. C. H., Fafarman, A. T., Hong, S. B., Rogers, M., Deady, L. W., Prusiner, S. B., Cohen, F. E. (2003). Potent inhibition of scrapie prion replication in cultured cells by bis-acridines. Proc. Natl. Acad. Sci. USA 100: 3416-3421 [Abstract] [Full Text]  
  • Bennion, B. J., Daggett, V. (2002). Protein Conformation and Diagnostic Tests: The Prion Protein. Clin. Chem. 48: 2105-2114 [Abstract] [Full Text]  
  • Ma, J., Wollmann, R., Lindquist, S. (2002). Neurotoxicity and Neurodegeneration When PrP Accumulates in the Cytosol. Science 298: 1781-1785 [Abstract] [Full Text]  
  • Perrier, V., Kaneko, K., Safar, J., Vergara, J., Tremblay, P., DeArmond, S. J., Cohen, F. E., Prusiner, S. B., Wallace, A. C. (2002). Dominant-negative inhibition of prion replication in transgenic mice. Proc. Natl. Acad. Sci. USA 99: 13079-13084 [Abstract] [Full Text]  
  • Forloni, G., Iussich, S., Awan, T., Colombo, L., Angeretti, N., Girola, L., Bertani, I., Poli, G., Caramelli, M., Grazia Bruzzone, M., Farina, L., Limido, L., Rossi, G., Giaccone, G., Ironside, J. W., Bugiani, O., Salmona, M., Tagliavini, F. (2002). Tetracyclines affect prion infectivity. Proc. Natl. Acad. Sci. USA 99: 10849-10854 [Abstract] [Full Text]  
  • Brown, P. (2002). Drug therapy in human and experimental transmissible spongiform encephalopathy. Neurology 58: 1720-1725 [Abstract] [Full Text]  
  • Korth, C., May, B. C. H., Cohen, F. E., Prusiner, S. B. (2001). Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc. Natl. Acad. Sci. USA 98: 9836-9841 [Abstract] [Full Text]  
  • Horiuchi, M., Baron, G. S., Xiong, L.-W., Caughey, B. (2001). Inhibition of Interactions and Interconversions of Prion Protein Isoforms by Peptide Fragments from the C-terminal Folded Domain. J. Biol. Chem. 276: 15489-15497 [Abstract] [Full Text]  
  • Gu, Y., Fujioka, H., Mishra, R. S., Li, R., Singh, N. (2002). Prion Peptide 106-126 Modulates the Aggregation of Cellular Prion Protein and Induces the Synthesis of Potentially Neurotoxic Transmembrane PrP. J. Biol. Chem. 277: 2275-2286 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»