Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis.

Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Research Abstract Details 

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Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Abstract Text:

Subhabrata Basu,Maradumane L Mohan,Xiu Luo,Bishwajit Kundu,Qingzhong Kong,Neena Singh,

The principal infectious and pathogenic agent in all prion disorders is a beta-sheet-rich isoform of the cellular prion protein (PrP(C)) termed PrP-scrapie (PrP(Sc)). Once initiated, PrP(Sc) is self-replicating and toxic to neuronal cells, but the underlying mechanisms remain unclear. In this report, we demonstrate that PrP(C) binds iron and transforms to a PrP(Sc)-like form (*PrP(Sc)) when human neuroblastoma cells are exposed to an inorganic source of redox iron. The *PrP(Sc) thus generated is itself redox active, and it induces the transformation of additional PrP(C), simulating *PrP(Sc) propagation in the absence of brain-derived PrP(Sc). Moreover, limited depletion of iron from prion disease-affected human and mouse brain homogenates and scrapie-infected mouse neuroblastoma cells results in 4- to 10-fold reduction in proteinase K (PK)-resistant PrP(Sc), implicating redox iron in the generation, propagation, and stability of PK-resistant PrP(Sc). Furthermore, we demonstrate increased redox-active ferrous iron levels in prion disease-affected brains, suggesting that accumulation of PrP(Sc) is modulated by the combined effect of imbalance in brain iron homeostasis and the redox-active nature of PrP(Sc). These data provide information on the mechanism of replication and toxicity by PrP(Sc), and they evoke predictable and therapeutically amenable ways of modulating PrP(Sc) load.

Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Publishing Authors By Initials

S Basu,ML Mohan,X Luo,B Kundu,Q Kong,N Singh,

For similar complex mixtures: tissue extracts research abstracts see: complex mixtures: tissue extracts research

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Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular biology of the cell

VOLUME: 18

Page Numbers: 3302-12

Journal Abbreviation: Mol. Biol. Cell

ISSN: 1059-1524

DAY: 13

MONTH: 06

YEAR: 2007

Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9201390

Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Keywords Mesh Terms:

KEYWORDS: Tissue Extracts

MESH TERMS: metabolism

Chemical & Substance for Abstract: Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis. Information

Substance Name: Endopeptidase K

Registry Number: EC 3.4.21.64

Grant and Affiliation Information for Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis.

AFFILIATION: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS-39089

ACRONYM: NS

MEDLINETA: Mol Biol Cell

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