HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 46, 34848-34858, November 17, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/46/34848    most recent M602238200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yuan, J. Articles by Zou, W.-Q. Search for Related Content PubMed PubMed Citation Articles by Yuan, J. Articles by Zou, W.-Q. Social Bookmarking                      What's this?

Insoluble Aggregates and Protease-resistant Conformers of Prion Protein in Uninfected Human Brains^*

Jue Yuan, Xiangzhu Xiao, John McGeehan¹, Zhiqian Dong, Ignazio Cali, Hisashi Fujioka, Qingzhong Kong, Geoff Kneale, Pierluigi Gambetti, and Wen-Quan Zou²

From the Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio 44106 and the Biophysics Laboratories, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth PO1 2DT, United Kingdom

Aggregated prion protein (PrP^Sc), which is detergent-insoluble and partially proteinase K (PK)-resistant, constitutes the major component of infectious prions that cause a group of transmissible spongiform encephalopathies in animals and humans. PrP^Sc derives from a detergent-soluble and PK-sensitive cellular prion protein (PrP^C) through an -helix to -sheet transition. This transition confers on the PrP^Sc molecule unique physicochemical and biological properties, including insolubility in nondenaturing detergents, an enhanced tendency to form aggregates, resistance to PK digestion, and infectivity, which together are regarded as the basis for distinguishing PrP^Sc from PrP^C. Here we demonstrate, using sedimentation and size exclusion chromatography, that small amounts of detergent-insoluble PrP aggregates are present in uninfected human brains. Moreover, PK-resistant PrP core fragments are detectable following PK treatment. This is the first study that provides experimental evidence supporting the hypothesis that there might be silent prions lying dormant in normal human brains.

Received for publication, March 9, 2006 , and in revised form, September 18, 2006.

^* This work was supported by a Career Developmental Award from STERIS Co. (to W. Q. Z.) and National Institutes of Health Grants AG-14359 and AG08702, the Center for Disease Control and Prevention Contract UR8/CCU515004, and the Britton Fund (to P. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Current address: EMBL, 6 Rue Jules Horowitz, 38042 Grenoble, France.

² To whom correspondence should be addressed. Tel.: 216-368-8993; Fax: 216-368-2546; E-mail: wenquan.zou{at}case.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Xiao, L. Miravalle, J. Yuan, J. McGeehan, Z. Dong, R. Wyza, G. T. MacLennan, A. M. Golichowski, G. Kneale, N. King, et al. Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease Am. J. Pathol., May 1, 2009; 174(5): 1602 - 1608. [Abstract] [Full Text] [PDF]

				F. Martucci, P. Acutis, M. Mazza, S. Nodari, S. Colussi, C. Corona, S. Barocci, A. Gabrielli, M. Caramelli, C. Casalone, et al. Detection of typical and atypical bovine spongiform encephalopathy and scrapie prion strains by prion protein motif-grafted antibodies J. Gen. Virol., April 1, 2009; 90(4): 1048 - 1053. [Abstract] [Full Text] [PDF]

				R. Chiesa, P. Piccardo, E. Biasini, B. Ghetti, and D. A. Harris Aggregated, Wild-Type Prion Protein Causes Neurological Dysfunction and Synaptic Abnormalities J. Neurosci., December 3, 2008; 28(49): 13258 - 13267. [Abstract] [Full Text] [PDF]

				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]

				P. Brown Transmissible spongiform encephalopathy in the 21st century: Neuroscience for the clinical neurologist Neurology, February 26, 2008; 70(9): 713 - 722. [Full Text] [PDF]

				J. C. Geoghegan, P. A. Valdes, N. R. Orem, N. R. Deleault, R. A. Williamson, B. T. Harris, and S. Supattapone Selective Incorporation of Polyanionic Molecules into Hamster Prions J. Biol. Chem., December 14, 2007; 282(50): 36341 - 36353. [Abstract] [Full Text] [PDF]