Journal of Cell Science 116, e1304 (2003)
Copyright © 2003 The Company of Biologists Limited
Knocking down prions
Prion diseases, such as Creutzfeld-Jakob disease (CJD) in humans, scrapie
in sheep and BSE in cattle, are characterized by formation of insoluble
aggregates containing a protease-resistant form (PrP-res) of the cellular
prion protein (PrP-sen) in the central nervous system. Development of these
diseases requires endogenous PrP-sen, which the infectious PrP-res seems able
to convert into more PrP-res. Elimination of PrP-sen might therefore represent
an effective way of combating PrP-res. On
p. 2775, Joëlle Chabry
and co-workers reveal that RNAi technology can do just that. They demonstrate
that transfection of scrapie-infected neuroblastoma cells with a 21-nucleotide
small interfering RNA (siRNA) directed against the Prnp gene (which
encodes PrP-sen) efficiently and specifically inhibits PrP-sen synthesis and
drastically reduces accumulation of PrP-res. Importantly, the authors
demonstrate that the silencing effect is independent of cell type and scrapie
strain, and the siRNA does not appear to be cytotoxic. Their findings indicate
that RNAi has potential as a therapeutic approach for treatment of prion
diseases and perhaps other diseases characterized by accumulation of insoluble
protein aggregates, such as Alzheimer's and Huntington's disease.
Related articles in JCS:
- Specific inhibition of pathological prion protein accumulation by small interfering RNAs
- Nathalie Daude, Mathieu Marella, and Joëlle Chabry
JCS 2003 116: 2775-2779.
[Abstract]
[Full Text]
