Selective neuronal targeting in prion disease

Stephen J. DeArmond*, Henry Sánchez, Fruma Yehiely, Yin Qiu, Anne Ninchak-Casey, Valerie Daggett, Almerian P. Camerino, Juliana Cayetano, Mark Rogers, Darlene Groth, Marilyn Torchia, Patrick Tremblay, Michael R. Scott, Fred E. Cohen, Stanley B. Prusiner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

The pattern of scrapie prion protein (PrP(Sc)) accumulation in the brain is different for each prion strain. We tested whether the PrP(Sc) deposition pattern is influenced by the Asn-linked oligosaccharides of PrP(c) in transgenic mice. Deletion of the first oligosaccharide altered PrP(c) trafficking and prevented infection with two prion strains. Deletion of the second did not alter PrP(c) trafficking, permitted infection with one prion strain, and had a profound effect on the PrP(Sc) deposition pattern. Our data raise the possibility that glycosylation can modify the conformation of PrP(c). Glycosylation could affect the affinity of PrP(c) for a particular conformer of PrP(Sc) thereby determining the rate of nascent PrP(Sc) formation and the specific patterns of PrP(Sc) deposition.

Original languageEnglish (US)
Pages (from-to)1337-1348
Number of pages12
JournalNeuron
Volume19
Issue number6
DOIs
StatePublished - Dec 1997

ASJC Scopus subject areas

  • Neuroscience(all)

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