Abstract:
:While prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently demonstrated resistance to prion infection in mice overexpressing a mutated prion protein (PrP) carrying a specific amino acid substitution characteristic of canids. Here, we show that coexpression of this mutated PrP and wild-type mouse PrP in transgenic mice inoculated with different mouse-adapted prion strains (22 L, ME7, RML, and 301C) significantly increases survival times (by 45 to 113%). These data indicate that this amino acid substitution confers a dominant-negative effect on PrP, attenuating the conversion of PrPC to PrPSc and delaying disease onset without altering the neuropathological properties of the prion strains. Taken together, these findings have important implications for the development of new treatment approaches for prion diseases based on dominant-negative proteins.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Otero A,Bolea R,Hedman C,Fernández-Borges N,Marín B,López-Pérez Ó,Barrio T,Eraña H,Sánchez-Martín MA,Monzón M,Badiola JJ,Castilla Jdoi
10.1007/s12035-017-0832-8subject
Has Abstractpub_date
2018-07-01 00:00:00pages
6182-6192issue
7eissn
0893-7648issn
1559-1182pii
10.1007/s12035-017-0832-8journal_volume
55pub_type
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