QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Movies Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Künzi, V. Articles by Aguzzi, A. Search for Related Content PubMed PubMed Citation Articles by Künzi, V. Articles by Aguzzi, A.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 1, 2002, 22(17):7471-7477

Unhampered Prion Neuroinvasion despite Impaired Fast Axonal Transport in Transgenic Mice Overexpressing Four-Repeat Tau

Valérie Künzi^{1, *}, Markus Glatzel^{1, *}, Michel Y. Nakano², Urs F. Greber², Fred Van Leuven³, and Adriano Aguzzi¹

¹ Institute of Neuropathology, University Hospital Zürich, CH-8091 Zürich, Switzerland, ² Institute of Zoology, University of Zürich, CH-8093 Zürich, Switzerland, and ³ Experimental Genetics Group, Catholic University of Leuven, B-3000 Leuven, Belgium

Transmissible spongiform encephalopathies often are caused by peripheral uptake of infectious prions, and the peripheral nervous system is involved in prion spread to the brain. Although the cellular prion protein is subjected to fast axonal transport, the mechanism of intranerval transport of infectious prions is unclear. Here we administered prions intranervally to transgenic mice overexpressing the four-repeat human tau protein, which exhibit defective fast axonal transport. These mice showed unaltered neuroinvasion, suggesting that transport mechanisms distinct from fast axonal transport effect prion neuroinvasion along peripheral nerves. Surprisingly, scrapie-sick tau transgenic mice accumulated intraneuronal deposits of hyperphosphorylated tau protein. The coincidence of tau and prion pathology resembled Gerstmann-Sträussler-Scheinker syndrome. These findings identify tau pathology as a possible end stretch of prion-induced neurodegeneration.

Key words: transmissible spongiform encephalopathy; prion neuroinvasion; peripheral nervous system; impaired fast axonal transport; tau overexpression; tau hyperphosphorylation

---

^* V.K and M.G. contributed equally to this work.

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22177471-07$05.00/0

This article has been cited by other articles:

				G. G. Kovacs and H. Budka Prion Diseases: From Protein to Cell Pathology Am. J. Pathol., March 1, 2008; 172(3): 555 - 565. [Abstract] [Full Text] [PDF]

				C. Kratzel, D. Kruger, and M. Beekes Prion propagation in a nerve conduit model containing segments devoid of axons J. Gen. Virol., December 1, 2007; 88(12): 3479 - 3485. [Abstract] [Full Text] [PDF]

				C. Ersdal, M. J. Ulvund, A. Espenes, S. L. Benestad, P. Sarradin, and T. Landsverk Mapping PrPSc Propagation in Experimental and Natural Scrapie in Sheep with Different PrP Genotypes Veterinary Pathology, May 1, 2005; 42(3): 258 - 274. [Abstract] [Full Text] [PDF]

				D. Terwel, R. Lasrado, J. Snauwaert, E. Vandeweert, C. Van Haesendonck, P. Borghgraef, and F. Van Leuven Changed Conformation of Mutant Tau-P301L Underlies the Moribund Tauopathy, Absent in Progressive, Nonlethal Axonopathy of Tau-4R/2N Transgenic Mice J. Biol. Chem., February 4, 2005; 280(5): 3963 - 3973. [Abstract] [Full Text] [PDF]

				G. G. Kovacs, M. Preusser, M. Strohschneider, and H. Budka Subcellular Localization of Disease-Associated Prion Protein in the Human Brain Am. J. Pathol., January 1, 2005; 166(1): 287 - 294. [Abstract] [Full Text] [PDF]

				B. Zhang, M. Higuchi, Y. Yoshiyama, T. Ishihara, M. S. Forman, D. Martinez, S. Joyce, J. Q. Trojanowski, and V. M.-Y. Lee Retarded Axonal Transport of R406W Mutant Tau in Transgenic Mice with a Neurodegenerative Tauopathy J. Neurosci., May 12, 2004; 24(19): 4657 - 4667. [Abstract] [Full Text] [PDF]

				F. Archer, C. Bachelin, O. Andreoletti, N. Besnard, G. Perrot, C. Langevin, A. Le Dur, D. Vilette, A. Baron-Van Evercooren, J.-L. Vilotte, et al. Cultured Peripheral Neuroglial Cells Are Highly Permissive to Sheep Prion Infection J. Virol., January 1, 2004; 78(1): 482 - 490. [Abstract] [Full Text] [PDF]

				A. Mironov Jr, D. Latawiec, H. Wille, E. Bouzamondo-Bernstein, G. Legname, R. A. Williamson, D. Burton, S. J. DeArmond, S. B. Prusiner, and P. J. Peters Cytosolic Prion Protein in Neurons J. Neurosci., August 6, 2003; 23(18): 7183 - 7193. [Abstract] [Full Text] [PDF]

				A. Aguzzi, F. L Heppner, M. Heikenwalder, M. Prinz, K. Mertz, H. Seeger, and M. Glatzel Immune system and peripheral nerves in propagation of prions to CNS Br. Med. Bull., June 1, 2003; 66(1): 141 - 159. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help