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

doi:10.1016/S0896-6273(00)80424-9

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

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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 language	English (US)
Pages (from-to)	1337-1348
Number of pages	12
Journal	Neuron
Volume	19
Issue number	6
DOIs	https://doi.org/10.1016/S0896-6273(00)80424-9
State	Published - Dec 1997

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0896-6273(00)80424-9

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@article{adc187b7047a4a11a64c6304aa530124,

title = "Selective neuronal targeting in prion disease",

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.",

author = "DeArmond, {Stephen J.} and Henry S{\'a}nchez and Fruma Yehiely and Yin Qiu and Anne Ninchak-Casey and Valerie Daggett and Camerino, {Almerian P.} and Juliana Cayetano and Mark Rogers and Darlene Groth and Marilyn Torchia and Patrick Tremblay and Scott, {Michael R.} and Cohen, {Fred E.} and Prusiner, {Stanley B.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (NS14069, AG08967, AG02132, and NS22786) as well as by gifts from the Sherman Fairchild Foundation, the G. Harold and Leila Y. Mathers Foundation, and Centeon. ",

year = "1997",

month = dec,

doi = "10.1016/S0896-6273(00)80424-9",

language = "English (US)",

volume = "19",

pages = "1337--1348",

journal = "Neuron",

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T1 - Selective neuronal targeting in prion disease

AU - DeArmond, Stephen J.

AU - Sánchez, Henry

AU - Yehiely, Fruma

AU - Qiu, Yin

AU - Ninchak-Casey, Anne

AU - Daggett, Valerie

AU - Camerino, Almerian P.

AU - Cayetano, Juliana

AU - Rogers, Mark

AU - Groth, Darlene

AU - Torchia, Marilyn

AU - Tremblay, Patrick

AU - Scott, Michael R.

AU - Cohen, Fred E.

AU - Prusiner, Stanley B.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (NS14069, AG08967, AG02132, and NS22786) as well as by gifts from the Sherman Fairchild Foundation, the G. Harold and Leila Y. Mathers Foundation, and Centeon.

PY - 1997/12

Y1 - 1997/12

N2 - 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.

AB - 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.

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JO - Neuron

JF - Neuron

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Selective neuronal targeting in prion disease

Abstract

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