Influence of Water, Fat, and Glycerol on the Mechanism of Thermal Prion Inactivation

Müller, Henrik; Stitz, Lothar; Wille, Holger; Prusiner, Stanley B.; Riesner, Detlev

doi:10.1074/jbc.m706883200

Cited by 19 publications

(35 citation statements)

References 49 publications

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“…MBM was prepared from the offal of sheep, cattle, pigs, and chickens as a high-protein nutritional supplement. In the late 1970s, the hydrocarbon-solvent extraction method used in the rendering of offal began to be abandoned, resulting in MBM with a much higher fat content (Wilesmith et al 1991;Muller et al 2007). It is now thought that this change allowed scrapie prions from sheep or low levels of bovine prions generated sporadically to survive the rendering process, resulting in the widespread infection of cattle.…”

Section: Prion Diseases Of Animalsmentioning

confidence: 99%

Prions

Colby¹,

Prusiner²

2011

Cold Spring Harbor Perspectives in Biology

458

390

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Section: Prion Diseases Of Animalsmentioning

confidence: 99%

Prions

Colby¹,

Prusiner²

2011

Cold Spring Harbor Perspectives in Biology

458

390

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“…A blank spectrum for cuvette and buffer was subtracted from each spectrum. Satisfactory CD ellipticities of recPrP-amyloid were only obtained after increasing amyloid solubility by gentle sonication of 1 mg ml -1 PrP in presence of 0.12 % (vol/vol) SDS with a Misonix sonicator 3000 at 240 W for 1 min at <25 C. 66 Neither sonication only nor SDStreatment only did result in measurable ellipticity. An influence of sonication or SDS-treatment on the secondary structure of amyloid fibrils is assumed to be negligible.…”

Section: Circular Dichroism (Cd) Spectroscopymentioning

confidence: 99%

Progress towards structural understanding of infectious sheep PrP-amyloid

Müller

Brener

Andréoletti

et al. 2014

Prion

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The still elusive structural difference of non-infectious and infectious amyloid of the mammalian prion protein (PrP) is a major pending milestone in understanding protein-mediated infectivity in neurodegenerative diseases. Preparations of PrP-amyloid proven to be infectious have never been investigated with a high-resolution technique. All available models to date have been based on low-resolution data. Here, we establish protocols for the preparation of infectious samples of full-length recombinant (rec) PrP-amyloid in NMR-sufficient amounts by spontaneous fibrillation and seeded fibril growth from brain extract. We link biological and structural data of infectious recPrP-amyloid, derived from bioassays, atomic force microscopy, and solid-state NMR spectroscopy. Our data indicate a semi-mobile N-terminus, some residues with secondary chemical shifts typical of a-helical secondary structure in the middle part between »115 to »155, and a distinct b-sheet core C-terminal of residue »155. These findings are not in agreement with all current models for PrP-amyloid. We also provide evidence that samples seeded from brain extract may not differ in the overall arrangement of secondary structure elements, but rather in the flexibility of protein segments outside the b-core region. Taken together, our protocols provide an essential basis for the high-resolution characterization of non-infectious and infectious PrP-amyloid in the near future.

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“…Two scientific papers which were cited in support of the application were evaluated (Müller et al, 2006(Müller et al, , 2008 198, 30.7.2011, p. 3-22. infectivity (Müller et al, 2007) was also reviewed. In addition, unpublished data provided by other experts as well as a number of relevant scientific papers were considered during the assessment.…”

Section: Datamentioning

confidence: 99%

“…The two papers submitted by the applicant (Müller et al, 2006(Müller et al, , 2008 were assessed by the Panel, as well as a third paper (not provided by the applicant) but by the same authors that included additional data on the effect of heat treatment in different fat/glycerol/water mixtures on scrapie infectivity (Müller et al, 2007). Additional papers from the literature were evaluated but experimental conditions were not similar to those of the process under evaluation and therefore were not considered further.…”

Section: The Assessment Of the Experimental Model By The Publicationsmentioning

confidence: 99%

“…In the experiments described by Müller et al (2006Müller et al ( , 2007Müller et al ( , 2008) a laboratory inactivation model for PrP Sc was used that closely replicates the conditions applied in the industrial application submitted by the applicant. In this respect, the experimental outcomes regarding PrP Sc infectivity or degradation can be considered a good indicator of the industrial process.…”

Section: The Assessment Of the Experimental Model By The Publicationsmentioning

confidence: 99%

See 1 more Smart Citation

Scientific Opinion on a continuous multiple‐step catalytic hydro‐treatment for the processing of rendered animal fat (Category 1)

2015

EFS2

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An alternative method for the treatment of rendered animal fat (Category 1) intended for the production of renewable fuels by a continuous multi-step catalytic hydro-treatment process was assessed. The alternative method is based on a pre-treatment by degumming and bleaching followed by a hydro-treatment comprising three main processes: catalytic hydro-treatment, stripping and isomerisation. The minimum processing conditions are pressure 30 bar, temperature 265°C and retention time 20 minutes. Based on the outcome of previous EFSA Opinions and the expert evaluation, the BIOHAZ Panel considered that a reduction of six log 10 in the transmissible spongiform encephalopathy (TSE) agent by the alternative method is necessary to consider the process at least equivalent, for Category 1 animal by-products, to the processing methods previously approved. Experimental data in the reviewed literature showed that similar processes at temperatures between 160 and 200°C deliver at least a 6 log 10 reduction in TSE infectivity in 20 minutes. Thus, at least a similar level of reduction is expected to be produced by the alternative method proposed. This is in addition to the inactivation achieved by the pressure sterilisation method applied prior to the application of the alternative method. The treatment under assessment is considered to achieve the required level of TSE inactivation, as long as the critical limits of key parameters are achieved as specified by the applicant. The minimum retention time is a critical parameter. The applicant's estimate of minimum retention time is based on the reactor size and the flow rate of the material, but the real minimum time in actual processing conditions has not been determined. It should be confirmed that a minimum retention time of 20 minutes is achieved in all parts of Category 1 material under normal operational conditions in order to ensure the effectiveness of the treatment.

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Influence of Water, Fat, and Glycerol on the Mechanism of Thermal Prion Inactivation

Cited by 19 publications

References 49 publications

Prions

Prions

Progress towards structural understanding of infectious sheep PrP-amyloid

Scientific Opinion on a continuous multiple‐step catalytic hydro‐treatment for the processing of rendered animal fat (Category 1)

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