Prion protein allotype profiling by mass spectrometry
M. E. Schininà, B. Maras, F. Cardone, C. Mancone, S. Principe, M. A. Di Bari, P. Parchi, and M. Pocchiari
1Dipartimento di Scienze Biochimiche “A. Rossi
Fanelli”, Università La Sapienza, Roma, Italy; 2Laboratorio
di Virologia and 3Laboratorio di Medicina Veterinaria, Istituto Superiore
di Sanità, Roma, Italy; 4Dipartimento di Scienze Neurologiche,
Università di Bologna, Italy
Abstract: Prion diseases or transmissible spongiform
encephalopathies (TSEs) are fatal neurodegenerative pathologies characterized
by the formation in the central nervous system of the amyloid protein
PrPSc, which derives from a cellular precursor called PrPc.
Epidemiological and laboratory studies have shown that in species where
the PrPc gene is polymorphic, the genotype composition is
an important factor for the development of the disease. Identification
of PrPSc allotypes accumulated in the brain during the disease
proved valuable to investigate whether these polymorphisms are critical
for the pathological conversion. These analyses are complicated by the
heterogeneity and the insolubility of the prion amyloid extracted from
affected brains, which have been obviated by extensive digestion of
extracted fractions and analysis of peptide fragment composition. We
have developed an optimized protocol of liquid chromatography/mass spectrometry
(LC/MS) that can reliably map PrP peptides in digested fractions with
a low PrPSc/contaminants ratio. This approach has been successfully
applied to the analysis of amyloidogenesis in experimentally infected
PrP-heterozygous laboratory animals.
*Pure Appl.Chem. 75,
141419 (2003). An issue of reviews and research papers based on
lectures presented at the 23rd IUPAC International Symposium on the
Chemistry of Natural Products, Florence, Italy, 28 July 2 August 2002.
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