SEARCH VEGSOURCE:

 

 

Follow Ups | Post Followup | Back to Discussion Board | VegSource
See spam or
inappropriate posts?
Please let us know.
  




From: TSS ()
Subject: The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infections
Date: August 16, 2007 at 9:25 am PST

The EMBO Journal advance online publication 16 August 2007;
doi: 10.1038/sj.emboj.7601830


The CNS glycoprotein Shadoo has PrPC-like protective properties and displays
reduced levels in prion infections

EMBO Open


Joel C Watts1, 2, Bettina Drisaldi1, Vivian Ng1, Jing Yang1, Bob Strome1,
Patrick Horne1, Man-Sun Sy3, Larry Yoong1, Rebecca Young4, Peter
Mastrangelo1, Catherine Bergeron1, 2, Paul E Fraser1, 5, George A Carlson4,
Howard T J Mount1, 6, Gerold Schmitt-Ulms1, 2 and David Westaway1, 2, 7

1 Centre for Research in Neurodegenerative Diseases, University of Toronto,
Toronto, Canada
2 Department of Laboratory Medicine and Pathobiology, University of Toronto,
Toronto, Canada
3 Department of Pathology, School of Medicine, Case Western Reserve
University, Cleveland, OH, USA
4 McLaughlin Research Institute, Great Falls, MT, USA
5 Department of Medical Biophysics, University of Toronto, Toronto, Canada
6 Department of Medicine, University of Toronto, Toronto, Canada
7 Centre for Prions and Protein Folding Diseases, University of Alberta,
Alberta, Canada

To whom correspondence should be addressed
David Westaway, Centre for Prions and Protein Folding Diseases, University
of Alberta, Room 116, Environmental Engineering Building, Edmonton, Alberta,
Canada T6G 2M8. Tel.: +780 492 9377; Fax: +780 492 9352; E-mail:
david.westaway@ualberta.ca

Received 6 March 2007; Accepted 24 July 2007; Published online 16 August
2007.


Abstract

The cellular prion protein, PrPC, is neuroprotective in a number of settings
and in particular prevents cerebellar degeneration mediated by CNS-expressed
Doppel or internally deleted PrP ('PrP'). This paradigm has facilitated
mapping of activity determinants in PrPC and implicated a cryptic PrPC-like
protein, ''. Shadoo (Sho) is a hypothetical GPI-anchored protein encoded by
the Sprn gene, exhibiting homology and domain organization similar to the
N-terminus of PrP. Here we demonstrate Sprn expression and Sho protein in
the adult CNS. Sho expression overlaps PrPC, but is low in cerebellar
granular neurons (CGNs) containing PrPC and high in PrPC-deficient dendritic
processes. In Prnp0/0 CGNs, Sho transgenes were PrPC-like in their ability
to counteract neurotoxic effects of either Doppel or PrP. Additionally,
prion-infected mice exhibit a dramatic reduction in endogenous Sho protein.
Sho is a candidate for , and since it engenders a PrPC-like neuroprotective
activity, compromised neuroprotective activity resulting from reduced levels
may exacerbate damage in prion infections. Sho may prove useful in
deciphering several unresolved facets of prion biology.

Keywords: neuroprotection, prions, PrP, scrapie


http://www.nature.com/emboj/journal/vaop/ncurrent/abs/7601830a.html


SEE FULL TEXT ;

http://www.nature.com/emboj/journal/vaop/ncurrent/pdf/7601830a.pdf


Public release date: 16-Aug-2007


Contact: Bev Betkowski
beverly.betkowski@ualberta.ca
780-492-3808
University of Alberta

New prion protein discovered by Canadian scientists may offer insight into
mad cow disease

Scientists have discovered a new protein that may offer fresh insights into
brain function in mad cow disease. “Our team has defined a second prion
protein called ‘Shadoo’, that exists in addition to the well-known prion
protein called ‘PrP’ ” said Professor David Westaway, director of the Centre
for Prions and Protein Folding Diseases at the University of Alberta.

“For decades we believed PrP was a unique nerve protein that folded into an
abnormal shape and caused prion disease: end of story. This view is no
longer accurate,” Westaway adds.

The study was conducted jointly by the University of Toronto, University of
Alberta, Case Western Reserve University (Ohio) and the McLaughlin Research
Institute (Montana). The research is published today in the EMBO Journal and
represents a culmination of work initiated at the University of Toronto in
1999, and then continued more recently at the University of Alberta.

This is the first discovery since 1985 of a new brain prion protein. “A
second prion protein had been inferred by other research, based on indirect
studies and the examination of DNA sequences,” said lead author Joel Watts,
a graduate student at the University of Toronto’s Centre for Research in
Neurodegenerative Diseases. “But we not only demonstrate that this
theoretical protein really exists and shares several properties with healthy
PrP; we have also defined an unexpected alteration in prion infections.

“As the PrP molecule alters shape and accumulates in a prion-affected brain,
the Shadoo protein seems to disappear,” Watts added. Since proteins in a
living cell are the molecules “that do the work, this is likely to be
significant,” he said.

“Many facets of a prion disease like BSE are puzzling,” Westaway said. “The
puzzles include the cause of death of brain cells, the function of normal
prion proteins, and the rules governing emergence and spread of prions from
animal to animal. We believe the Shadoo protein can give us a fresh purchase
on these important questions.”

###
This research project was funded by the Canadian Institutes of Health
Research (CIHR) and the Natural Sciences and Engineering Research Council
(NSERC).

For more information, please contact:
Professor David Westaway
Centre for Prions and Protein Folding Diseases
Link: www.prioncentre.ca
University of Alberta
780-492-9024
David.westaway@ualberta.ca

Joel Watts BSc
Centre for Research in Neurodegenerative Diseases
Link: http://www.utoronto.ca/crnd/
University of Toronto
416-978-3408
Joel.watts@utoronto.ca


http://www.eurekalert.org/pub_releases/2007-08/uoa-npp081507.php


TSS





Follow Ups:



Post a Followup

Name:
E-mail: (optional)
Subject:

Comments:

Optional Link URL:
Link Title:
Optional Image URL: