NR ACKW
AU Ceciliani,F.; Pergami,P.
TI Infective proteins: the prion puzzle.
QU Current Protein & Peptide Science 2001 Sep; 2(3): 191-204
PT journal article; review; review, academic
AB According to the Koch postulates an infectious organism is the one that can be isolated from an host suffering from a disorder, can be propagated in laboratory, can cause the same disease when introduced in another host, and finally, can be re-isolated from the host itself. If we change the word "organism" with the word "protein" we have a quite exact description of prions. Prion related disorders are a very unique category of infectious diseases. The ethiology of the so-called prionoses is related to the conversion of a normal protein (PrPc, the cellular isoform of the prion protein) into a pathological form (the scrapie isoform of the prion protein, PrPsc) which is able to propagate. The striking difference between the two forms seems to consist in a conformational modification of a mainly alpha-helix structured PrPc into a mainly beta-sheet PrPsc. The latter forms amyloid-like fibrils which precipitate into insoluble aggregates leading to the neurodegenerative changes specific of Spongiform Encephalopathies. This review will focus on the structure of the prion proteins and on PrPc cellular cycle, and it will discuss some hypothesis about the protein biochemical function. Finally, the various molecular mechanisms proposed for the development of conformational modifications will be reviewed, i.e. how a protein can become infectious by simply changing its structure.
ZR 132
MH Animal; Human; Mice; Prion Diseases/*physiopathology/*transmission; Prions/genetics/*pathogenicity
AD Dipartimento di Patologia Animale, Igiene e Sanita Pubblica Veterinaria, Universita di Milano, Via Celoria 10, 20133 Milan, Italy. Fabrizio.Ceciliani@unimi.it
SP englisch
PO Niederlande