Regional mapping of prion proteins in brain.

Taraboulos, Albert; Jendroska, K.; Serban, Dan; Yang, Shu-Lian; DeArmond, Stephen J.; Prusiner, Stanley B.

doi:10.1073/pnas.89.16.7620

Cited by 304 publications

(210 citation statements)

References 34 publications

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“…Even fewer factors have been found to accelerate pathogenesis after i.c. administration of prions (LaCasse et al, 2008; Spinner (Taraboulos et al, 1992), detection of PrP C and PrP Sc by Western blot (Lau et al, 2007), and quantitation of PrP C by sandwich ELISA were performed as described previously. Immunohistochemistry for SAF84 (1:200), GFAP (1:1,000), and IBA1 (1:1,000) was performed on paraffin sections and detected with diaminobenzidine (Sigma-Aldrich).…”

Section: Discussionmentioning

confidence: 99%

Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner

Kranich¹,

Kräutler²,

Falsig³

et al. 2010

J Cell Biol

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Progressive accumulation of PrP(Sc), a hallmark of prion diseases, occurs when conversion of PrP(C) into PrP(Sc) is faster than PrP(Sc) clearance. Engulfment of apoptotic bodies by phagocytes is mediated by Mfge8 (milk fat globule epidermal growth factor 8). In this study, we show that brain Mfge8 is primarily produced by astrocytes. Mfge8 ablation induced accelerated prion disease and reduced clearance of cerebellar apoptotic bodies in vivo, as well as excessive PrP(Sc) accumulation and increased prion titers in prion-infected C57BL/6 × 129Sv mice and organotypic cerebellar slices derived therefrom. These phenotypes correlated with the presence of 129Sv genomic markers in hybrid mice and were not observed in inbred C57BL/6 Mfge8(-/-) mice, suggesting the existence of additional strain-specific genetic modifiers. Because Mfge8 receptors are expressed by microglia and depletion of microglia increases PrP(Sc) accumulation in organotypic cerebellar slices, we conclude that engulfment of apoptotic bodies by microglia may be an important pathway of prion clearance controlled by astrocyte-borne Mfge8.

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Section: Discussionmentioning

confidence: 99%

Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner

Kranich¹,

Kräutler²,

Falsig³

et al. 2010

J Cell Biol

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“…Distribution of PrP Sc depends on the prion strain and host species [52,124]. Certain specific combinations of strain and host may lead to PrP Sc induction/distribution in the blood and urine.…”

Section: Resultsmentioning

confidence: 99%

“…The tonsils may be used in humans, deer, and sheep [38,39,112,113,130,137,140], while the appendix has only been used for preclinical diagnosis of vCJD in humans [40,41,42,47,137]. Additionally, combination of the recently improved IHC analysis [using modified histoblot of paraffin-embedded tissue (PET) blot] with PK treatment or Western blotting has been introduced for detection of PrP Sc in cryosections and paraffin-embedded sections, respectively [92,114,124].…”

Section: Conventional Diagnostic Methods For Prion Diseasesmentioning

confidence: 99%

Recent Developments in Prion Disease Research: Diagnostic Tools and In Vitro Cell Culture Models

Sakudo

Nakamura

Ikuta

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. After prion infection, an abnormal isoform of prion protein (PrP Sc ) converts the cellular isoform of prion protein (PrP C ) into PrP Sc . PrP C -to-PrP Sc conversion leads to PrP Sc accumulation and PrP C deficiency, contributing etiologically to induction of prion diseases. Presently, most of the diagnostic methods for prion diseases are dependent on PrP Sc detection. Highly sensitive/accurate specific detection of PrP Sc in many different samples is a prerequisite for attempts to develop reliable detection methods. Towards this goal, several methods have recently been developed to facilitate sensitive and precise detection of PrP Sc , namely, protein misfolding cyclic amplification, conformation-dependent immunoassay, dissociation-enhanced lanthanide fluorescent immunoassay, capillary gel electrophoresis, fluorescence correlation spectroscopy, flow microbead immunoassay, etc. Additionally, functionally relevant prion-susceptible cell culture models that recognize the complexity of the mechanisms of prion infection have also been pursued, not only in relation to diagnosis, but also in relation to prion biology. Prion protein (PrP) gene-deficient neuronal cell lines that can clearly elucidate PrP C functions would contribute to understanding of the prion infection mechanism. In this review, we describe the trend in recent development of diagnostic methods and cell culture models for prion diseases and their potential applications in prion biology. Evidence of prion infections has been established by the accumulation of an abnormal isoform of prion protein (PrP Sc ) and/or infectivity after multiple passages [54,85,94,131]. In vitro conversion of the cellular isoform of prion protein (PrP C ) to form PrP Sc -like products has been demonstrated by incubating 35 S-labeled PrP C with PrP Sc . This produced a protease-resistant radioactive product with the mobility of protease-treated authentic PrP Sc [55]. This in vitro conversion confirms the species-[90] and strain-specificities [7] observed in vivo. However, because the yield is less stoichiometric than for PrP Sc [55], it has not been possible to determine whether or not an increase in infectivity occurred [55]. Recent progress in the development of diagnostic methods for PrP Sc detection has dramatically facilitated many approaches in prion biology. The protein misfolding cyclic amplification (PMCA) method deserves special mention [96]. Hitherto, it has not been possible to renature completely denatured prion preparations to an infectious state [79,81]; however, the novel PMCA approach enables in vitro amplification of infectious prions [16].The susceptibility of cell lines, such as N2a, in an in vitro cell culture assay to prion infections has been assessed by exposing the cells to serial dilutions of prion-infected mouse brain homogenates, and the dilution rate yielding negative outcome in a blotting assay for PrP Sc has been determined to be the infectivity level. Prion concentrations equivalent to those determined in an animal bioassay [9] have ...

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“…Distribution of PrP res deposition in the infected brain, as assessed by PETblot or histoblot can vary in a strain-dependent manner [127,137], raising the possibility that distinct strains multiply in distinct brain cell types [36]. Since the central nervous system is extremely complex, the basis of prion identity and diversity should be advantageously investigated in single cell lines faithfully propagating several strains of prions.…”

Section: Biological Properties Of Cell-passaged Prion Strainsmentioning

confidence: 99%

Cell models of prion infection

Vilette

2007

Vet. Res.

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-Due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. These include established cell lines, neuronal stem cells and primary neuronal cultures. While most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. These models have improved our knowledge on the molecular and cellular events controlling the conversion of the PrP C protein into abnormal isoforms and on the cell-to-cell spreading of prions. Infected cultured cells will also facilitate investigations on the molecular basis of strain identity and on the mechanisms that lead to neurodegeneration. The ongoing development of new cell models with improved characteristics will certainly be useful for a number of unanswered critical issues in the prion field.

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Regional mapping of prion proteins in brain.

Cited by 304 publications

References 34 publications

Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner

Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner

Recent Developments in Prion Disease Research: Diagnostic Tools and In Vitro Cell Culture Models

Cell models of prion infection

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