45th Article " Prion degradation pathways: potential for therapeutic intervention."

Nur fatmawati
16611047

Prion degradation pathways: potential for therapeutic intervention.

Lysosomal Proteolysis. The other major pathway of protein degradation in eukaryotic cells involves the uptake of proteins by lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases. A defining characteristic of the transmissible isoform of the prion protein (PrP(Sc)) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrP(Sc) by Western blot, ELISA or immunohistochemical detection. PK digestion has also been used to detect differences in prion strains. Thus, PK has been a crucial tool to detect and, thereby, control the spread of prions. PK has also been used as a tool to probe the structure of PrP(Sc). Mass spectrometry and antibodies have been used to identify PK cleavage sites in PrP(Sc). These results have been used to identify the more accessible, flexible stretches connecting the β-strand components in PrP(Sc). These data, combined with physical constraints imposed by spectroscopic results, were used to propose a qualitative model for the structure of PrP(Sc).