1887

Abstract

Prion diseases are characterized by the accumulation of an abnormal, proteinase K-resistant isoform of the prion protein, PrP, which is generated by a post-translational conversion of the protease-sensitive normal cell-surface glycoprotein PrP involving major conformational changes. The conversion is thought to occur at the plasma membrane or along the endocytic pathway towards the lysosome. PrP aggregates have been found to accumulate in secondary lysosomes. In our study, the activities of two major lysosomal cysteine proteases, cathepsins B and L, were found to be significantly increased in scrapie-infected Neuro2a cells compared with uninfected cells using biochemical and cytochemical methods. We hypothesize that lysosomal proteases may be involved in a ‘second autocatalytic loop’ of PrP formation, acting in concert with the well-known autocatalytic enhancement of PrP conversion in the presence of PrP.

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2003-08-01
2019-10-22
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