Based on the hypothesis that prion diseases are viral infections, early studies attempted, and failed, to slow progression of disease by boosting type I interferon responses (Gresser and Pattison, 1968; Field et al., 1969; Worthington, 1972; Gresser et al., 1983).
A species barrier, based on the fact that prions from one species can have a different enough shape to resist being co-opted by prions from another species, seems to protect many animals.
The mechanisms responsible for neuronal death in transmissible spongiform encephalopathies (TSEs) are still not completely understood, and at least two major hypotheses have been formulated, based on the peculiar aspects of prion protein biology.
The prion concept is based on the capacity of minute amounts of aggregated prion molecules to convert the soluble form into high molecular weight aggregates [28].
Notably, blood products were once also considered 'safe', based on the lack of detectable prions in vCJD using an inadequately sensitive mouse bioassay [21].
While FUS belongs to the top 15 proteins based on the similarity of its predicted prion-like domain to yeast prion domains, TDP-43 is only 63rd on this list (28, 61).
The pathogenesis of prion diseases is based on the presence of PrPSc, a protease-resistant isoform of the normal cellular prion protein called PrPC [1], [2].
Three capturable aptamers were designed based on the PrP aptamer, which binds to prion protein.
Structural interpretation of the affinity improvement was performed based on the crystal structure of the original prion binder in complex with the BoPrP (95 104) peptide by modeling the corresponding mutations.
In this work, we have developed a probabilistic model to predict prion domains based on the primary sequence of proteins.
