 |
From: TSS (216-119-144-8.ipset24.wt.net)
Subject: Protein-only prion proposal
Date: August 24, 2004 at 2:45 pm PST
-------- Original Message --------
Subject: Protein-only prion proposal
Date: Mon, 23 Aug 2004 21:28:06 -0500
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@UNI-KARLSRUHE.DE
######## Bovine Spongiform Encephalopathy #########
Protein-only prion proposal Stanley Prusiner first put forward the
protein-only hypothesis of prion
propagation in 1982. Now, 22 years
later, his research group has moved a
step closer to proving once and for all
that the infectious properties of prions
are due to the propagation of protein
misfolding. The present article from
Prusiners group comes close to being
this final proof , Claudio Soto
(University of Texas Medical Center,
TX, USA) told The Lancet Neurology.
However, a number of technical
issues minimise my enthusiasm.
Most experts agree that the
hypothesis would be proven if a
synthetic infectious protein engineered
in vitro was shown to be capable of
causing disease in vivo. Prusiners
team, which is based at the University
of California, San Francisco,
engineered Escherichia coli to express a
truncated version of mouse prion
protein; E Coli does not normally
produce prion proteins.
The researchers then folded the
protein into a beta-sheet rich conformation
that was likely to be infectious
and injected the protein into
transgenic mice that make the same
mutated prion fragment (called
TG9949 mice). 380 days later, one of
the mice showed symptoms of a prionlike
disease. By 660 days, all the mice
had neurological symptoms. Importantly,
TG9949 mice that were injected
with saline as controls failed to show
any signs of disease 620 days after
injection (Science 2004; 305: 67376).
Sotos main criticism is that
Prusiners team injected the synthetic
prion into a transgenic model that
expresses high levels of the truncated
version of the prion protein. It is
well-known in the field that most of
this type of animal develop clinical
signs and scrapie-like pathology
spontaneously , says Soto. The
injection of the recombinant protein
may have merely accelerated a process
that was set to occur spontaneously
anyway. For me it would have been
very convincing if the disease was
transmitted to wild-type animals in a
first passage. In addition, Soto notes
that the disease characteristics were
different to those normally obtained in
these animals.
Unsurprisingly, Prusiner is more
upbeat: The finding represents a
renaissance in prion biology. For the
first time, we can create prions in the
test tube, which will change the way
scientists do experiments in the field.
We now have a tool for exploring the
mechanism by which a protein can
spontaneously fold into a shape that
causes disease. James Butcher
Protein-only prion proposal
Neurology Vol 3 September 2004
http://neurology.thelancet.com TSS ######### http://mailhost-alt.rz.uni-karlsruhe.de/warc/bse-l.html ##########
Follow Ups:
Post a Followup
|
