|Biochem Biophys Res Commun. 2004 Aug 6;320(4):1240-6.
Effect of metal ions on de novo aggregation of
full-length prion protein.
Giese A, Levin J, Bertsch U, Kretzschmar H.
Zentrum fur Neuropathologie und Prionforschung,
Ludwig-Maximilians-Universitat, Munchen, Germany.
It is well established that the prion protein (PrP) contains metal ion
binding sites with specificity for copper. Changes in copper levels have
been suggested to influence incubation time in experimental prion disease.
Therefore, we studied the effect of heavy metal ions (Cu(2+), Mn(2+),
Ni(2+), Co(2+), and Zn(2+)) in vitro in a model system that utilizes changes
in the concentration of SDS to induce structural conversion and aggregation
of recombinant PrP. To quantify and characterize PrP aggregates, we used
fluorescently labelled PrP and cross-correlation analysis as well as
scanning for intensely fluorescent targets in a confocal single molecule
detection system. We found a specific strong pro-aggregatory effect of
Mn(2+) at low micromolar concentrations that could be blocked by nanomolar
concentration of Cu(2+). These findings suggest that metal ions such as
copper and manganese may also affect PrP conversion in vivo.
|Med Hypotheses. 2004;62(3):346-53.
Hypothesis of interference to superinfection between
bovine spastic paresis and bovine spongiform encephalopathy; suggestions
for experimentation, theoretical and practical interest.
DVM, 17, rue Jules Guesde, 59390 Lys-Lez-Lannoy, France.
Sub-acute transmissible spongiform encephalopathies (TSEs) or prion
diseases are diseases of little known etiology. The origin of these
diseases would appear to be an abnormal protease-resistant prion protein
(PrP(res)) which would be infectious by directly inducing its defective
conformation to the normal native protein (PrP(C)). This hypothesis does
not account for certain aspects of TSEs, such as interference to
superinfection: in laboratory animals, inoculation by means of an
attenuated strain with a long incubation period protects against later
infection by a very virulent strain with a short incubation period. The
hypothesis is put forward that there exists a possibility of interference
to superinfection between neurodegenerative diseases of unknown origin,
thought to be similar to TSEs, and a later infection by a TSE. The study
of this interference between bovine spastic paresis (BSP) and bovine
spongiform encephalopathy (BSE) could be used as a model for this
hypothesis. BSP is a very rare disease among cattle, of unknown etiology;
it is curable, in the very early stages, by using tryptophan and
especially lithium, potentiated by copper and manganese. An etiology close
to that of TSEs has been suggested on several occasions. If interference
could be demonstrated between BSP and BSE, interesting data would be
provided concerning the etiology, the pathogenesis and possibly the
treatment and prevention of these diseases. Notably, such data could lead
to the development of a treatment and a prevention with lithium and amino
acids precursors of neuromediators (tryptophan, tyrosine, glutamic acid,
etc.), as well as the developing of a vaccine to combat TSEs, especially
BSE and scrapie.
Création : 04 octobre 2004
Révision : 07 mars 2005