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From: TSS (router.douglasguardian.com)
Subject: A prion lexicon (out of control)
Date: January 9, 2005 at 4:00 pm PST

-------- Original Message --------
Subject: A prion lexicon (out of control)
Date: Sun, 9 Jan 2005 18:00:39 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE


##################### Bovine Spongiform Encephalopathy #####################

Correspondence


A prion lexicon (out of control)

In the beginning, there was the prion, a dyslexic acronym for
proteinaceous-infectious particle. In short order came PrP, an
abbreviation for prion protein (or perhaps proteinase-resistant protein)
and PrP 27-30, because the proteinase-treated protein had a molecular
weight of about 27-30 KDa. 04cor_10121 When it was
discovered that this protein was a pathologically misfolded version of a
normal cellular protein, the term prion began to be used by different
authors to indicate only the normal protein, only the abnormal protein,
or both forms of the protein, causing a degree of confusion that
continues to the present day. Also, the pairing of PrPc (for normal
cellular) and PrPSc (for scrapie-infected) came into widespread use, but
it is manifestly inappropriate to so designate the protein in different
kinds of transmissible spongiform encephalopathies, and thus was spawned
an alphabet soup of PrPs: PrPCJD, PrPGSS, PrPFFI, PrPBSE, PrPCWD, and
PrPTME. Because the normal protein was proteinase sensitive and the
misfolded protein was proteinase-resistant, the generically satisfying
PrPsen and PrPres twins were born,1 which for some time were the most
accurate representations of prion terminology (although PrPsen is a
contradiction in terms if PrP is understood in the sense of
proteinase-resistant protein). However, the discovery of
disease-specific protein species with intermediate proteinase
sensitivities has led to the birth of two new terms--PrPu (for partially
unfolded intermediate),2 and the fraternal twins, sPrPSc and rPrPSc.3
PrPu will probably be stillborn because the letter u could also signify
urinary, and become immersed in the current confusion that surrounds
urinary PrP studies, and the s and r twins may not survive infancy. In
an attempt to achieve some sort of comprehensive simplification of the
entire issue, yet another abbreviation has recently appeared in
print--PrPd (for disease-specific).4 Though accurate, it seems almost
too generic, lacking the necessary panache to have any real staying
power, and for proper balance, it would need a triangulation with PrPn
(normal) and PrPdsi (disease-specific intermediate) to accommodate the s
and r PrP's. In fact, it has already been subverted by a
reinterpretation of PrPsc as disease-causing isoform by the same group
that 20 years ago gave us its original designation as scrapie prion.5
Given the pressure from journals to save space, the ubiquitous use of
abbreviations in medical literature has produced setbacks both to ease
of reading and comprehension, but if abbreviations must be used, the
best pairing would seem to be PrPC for the normal cellular protein, and
PrPTSE for any of its disease-specific conformers. One might even revert
to plain English and dare to use actual words, like normal cellular
protein, transition protein (molten globule), and misfolded protein (or
amyloid protein), reducing the prion lexicon to a level that does not
intimidate by its arcane and often inaccurate terminology, and could be
understood by readers both within and without the specialty. We declare
that we have no conflict of interest.

*Paul Brown, Larisa Cervenakova

paulwbrown@comcast.net *7815 Exeter Road, Bethesda, MA 20814, USA (PB);
and Jerome H Holland Laboratory, American Red Cross, Rockville, MA, USA
(LC) 1 Caughey B, Neary K, Duller R, et al. Normal and
scrapie-associated forms of prion protein differ in their sensitivities
to phospholipase and proteases in intact neuroblastoma cells. J Virol
1990; 64: 1093-101. [PubMed

] 2 Politopolou G. Experimental approaches to TSE prevention via
inhibition of prion formation. Prot Peptide Lett
2004; 11: 249-55. [PubMed

] 3 Tremblay P, Ball HL, Kaneko K, et al. Mutant PrPSc conformers
induced by a synthetic peptide and several prion strains. J Virol
2004; 78: 2088-99. [PubMed

] 4 Jeffrey M, Martin S, Gonzalez L. Cell- associated variants of
disease-specific prion protein immunolabelling are found in different
sources of sheep transmissible spongiform encephalopathy. J Gen Virol
2003; 84: 1033-45. [PubMed

] 5 Serban A, Legname G, Hansen K, Kovaleva N, Prusiner SB.
Immunoglobulins in urine of hamsters with scrapie. J Biol Chem
2004; 279: 48817-20. [PubMed
]

TSS

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