scholarly journals Mammalian  prions

Prion ◽  
2011 ◽  
Vol 5 (2) ◽  
pp. 84-87 ◽  
Author(s):  
Jimmy Savistchenko ◽  
Zaira E. Arellano-Anaya ◽  
Olivier Andréoletti ◽  
Didier Vilette
Keyword(s):  
Mammalian Prions

scholarly journals A yeast-based assay to isolate drugs active against mammalian prions

Methods ◽  
2006 ◽  
Vol 39 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Stéphane Bach ◽  
Déborah Tribouillard ◽  
Nicolas Talarek ◽  
Nathalie Desban ◽  
Fabienne Gug ◽  
...  
Keyword(s):  
Mammalian Prions

scholarly journals Mammalian Prions Generated from Bacterially Expressed Prion Protein in the Absence of Any Mammalian Cofactors

2010 ◽  
Vol 285 (19) ◽  
pp. 14083-14087 ◽  
Author(s):  
Jae-Il Kim ◽  
Ignazio Cali ◽  
Krystyna Surewicz ◽  
Qingzhong Kong ◽  
Gregory J. Raymond ◽  
...  
Keyword(s):  
Prion Protein ◽  
Mammalian Prions

scholarly journals Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

2016 ◽  
Vol 473 (23) ◽  
pp. 4399-4412 ◽  
Author(s):  
Alana M. Thackray ◽  
Olivier Andreoletti ◽  
Raymond Bujdoso
Keyword(s):  
Brain Homogenate ◽  
Infected Sheep ◽  
Mammalian Host ◽  
Infected Blood ◽  
Clinical Phase ◽  
Prion Infectivity ◽  
Sheep Brain ◽  
Blood Fraction ◽  
Transgenic Drosophila ◽  
Mammalian Prions

In pursuit of a tractable bioassay to assess blood prion infectivity, we have generated prion protein (PrP) transgenic Drosophila, which show a neurotoxic phenotype in adulthood after exposure to exogenous prions at the larval stage. Here, we determined the sensitivity of ovine PrP transgenic Drosophila to ovine prion infectivity by exposure of these flies to a dilution series of scrapie-infected sheep brain homogenate. Ovine PrP transgenic Drosophila showed a significant neurotoxic response to dilutions of 10−2 to 10−10 of the original scrapie-infected sheep brain homogenate. Significantly, we determined that this prion-induced neurotoxic response in ovine PrP transgenic Drosophila was transmissible to ovine PrP transgenic mice, which is indicative of authentic mammalian prion detection by these flies. As a consequence, we considered that PrP transgenic Drosophila were sufficiently sensitive to exogenous mammalian prions to be capable of detecting prion infectivity in the blood of scrapie-infected sheep. To test this hypothesis, we exposed ovine PrP transgenic Drosophila to scrapie-infected plasma, a blood fraction notoriously difficult to assess by conventional prion bioassays. Notably, pre-clinical plasma from scrapie-infected sheep induced neurotoxicity in PrP transgenic Drosophila and this effect was more pronounced after exposure to samples collected at the clinical phase of disease. The neurotoxic phenotype in ovine PrP transgenic Drosophila induced by plasma from scrapie-infected sheep was transmissible since head homogenate from these flies caused neurotoxicity in recipient flies during fly-to-fly transmission. Our data show that PrP transgenic Drosophila can be used successfully to bioassay prion infectivity in blood from a prion-diseased mammalian host.

scholarly journals Structure of an infectious mammalian prion

2021 ◽  
Author(s):  
Allison Kraus ◽  
Forrest Hoyt ◽  
Cindi L. Schwartz ◽  
Bryan Hansen ◽  
Andrew G. Hughson ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Prion Proteins ◽  
Beta Sheets ◽  
Infectious Agents ◽  
Biophysical Properties ◽  
Amyloidogenic Proteins ◽  
Cryo Electron Microscopy ◽  
Polypeptide Backbone ◽  
Mammalian Prions ◽  
Lethal Doses

ABSTRACTClassical mammalian prions are assemblies of prion protein molecules that are extraordinarily transmissible, with a microgram of protein containing up to 108 lethal doses of infectivity1,2. Unlike most other pathologic and amyloidogenic proteins, prions typically contain glycolipid anchors 3 and abundant asparagine‐linked glycans4‐6. The infectious nature, complexity, and biophysical properties of prions have complicated structural analyses and stymied any prior elucidation of 3D conformation at the polypeptide backbone level7. Here we have determined the structure of the core of a fully infectious, brain‐derived prion by cryo‐electron microscopy with ∼3.1 Å resolution. The purified prions are amyloid fibrils comprised of monomers assembled with parallel in‐register intermolecular beta sheets and connecting chains. Residues ∼95‐227 of each monomer provide one rung of the ordered fibril core, with the glycans and glycolipid anchor projecting from the lateral surfaces of the fibril. The fibril ends, where prion growth occurs, are formed by single monomers in an extended serpentine combination of β‐ arches, a Greek key, and loops that presumably template the refolding of incoming monomers. Our results describe an atomic model to underpin detailed molecular hypotheses of how pathologic prion proteins can propagate as infectious agents, and how such propagation and associated pathogenesis might be impeded.

scholarly journals Generating Bona Fide Mammalian Prions with Internal Deletions

2016 ◽  
Vol 90 (15) ◽  
pp. 6963-6975 ◽  
Author(s):  
Carola Munoz-Montesino ◽  
Christina Sizun ◽  
Mohammed Moudjou ◽  
Laetitia Herzog ◽  
Fabienne Reine ◽  
...  
Keyword(s):  
De Novo ◽  
Alpha Helix ◽  
Transmissible Spongiform Encephalopathies ◽  
Specific Information ◽  
Beta Sheet ◽  
Internal Deletion ◽  
C Terminus ◽  
Parkinson’S Diseases ◽  
Bona Fide ◽  
Mammalian Prions

ABSTRACTMammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating andde novoinfectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions.IMPORTANCEPrions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative disorders. Other aggregation-prone proteins appear to have a prion-like mode of expansion in brains, such as in Alzheimer's or Parkinson's diseases. To date, the resolution of prion structure remains elusive. Thus, to genetically define the landscape of regions critical for prion conversion, we tested the effect of short deletions. We found that, surprisingly, removal of a portion of PrP, the C terminus of alpha-helix H2, did not hamper prion formation but generated infectious agents with an internal deletion that showed characteristics essentially similar to those of original infecting strains. Thus, we demonstrate that completeness of the residues inside prions is not necessary for maintaining infectivity and the main strain-specific information, while reporting one of the few if not the only bona fide prions with an internal deletion.

scholarly journals Mammalian prions

Prion ◽  
2013 ◽  
Vol 7 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Muhammad Khalid Salamat ◽  
Carola Munoz-Montesino ◽  
Mohammed Moudjou ◽  
Human Rezaei ◽  
Hubert Laude ◽  
...  
Keyword(s):  
Mammalian Prions

scholarly journals Molecular Basis of Barriers for Interspecies Transmissibility of Mammalian Prions

2004 ◽  
Vol 14 (1) ◽  
pp. 139-145 ◽  
Author(s):  
David L Vanik ◽  
Krystyna A Surewicz ◽  
Witold K Surewicz
Keyword(s):  
Molecular Basis ◽  
Mammalian Prions

Structure of mammalian prions

2009 ◽  
Vol 4 (3) ◽  
pp. 295-307 ◽  
Author(s):  
Jesús R Requena
Keyword(s):  
Mammalian Prions
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