In FY2013: 1) We have worked toward a better understanding of prion structure by initiating the application of new (to our lab) biochemical, immunological, spectroscopic, electron microscopic, and computational approaches to defining the structure of infectious prions. We have developed new models of prion structure is being built and evaluated based on our own new data, as well as published reports. These models are based on parallel-in-register beta sheet architectures, partial versions of which have been proposed by others. These developments are in progress and are expected to lead to significant discoveries soon. 2) We have assessed the role of normal prion protein in responses to stimulators of toll-like receptor ligands and have not found any significant effects. 3) We have probed the role of normal prion protein in the experimental autoimmune encephalomyelitis in mice of the C57/BL background and found no significant effect.

Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2013
Total Cost
$524,834
Indirect Cost
City
State
Country
Zip Code
Cracco, Laura; Notari, Silvio; Cali, Ignazio et al. (2017) Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type. Sci Rep 7:38280
Wang, Fei; Wang, Xinhe; OrrĂº, Christina D et al. (2017) Self-propagating, protease-resistant, recombinant prion protein conformers with or without in vivo pathogenicity. PLoS Pathog 13:e1006491
Bett, Cyrus; Lawrence, Jessica; Kurt, Timothy D et al. (2017) Enhanced neuroinvasion by smaller, soluble prions. Acta Neuropathol Commun 5:32
Groveman, Bradley R; Raymond, Gregory J; Campbell, Katrina J et al. (2017) Role of the central lysine cluster and scrapie templating in the transmissibility of synthetic prion protein aggregates. PLoS Pathog 13:e1006623
Kraus, Allison; Raymond, Gregory J; Race, Brent et al. (2017) PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions. J Virol 91:
Hughson, Andrew G; Race, Brent; Kraus, Allison et al. (2016) Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid. PLoS Pathog 12:e1005914
Alibhai, James; Blanco, Richard A; Barria, Marcelo A et al. (2016) Distribution of Misfolded Prion Protein Seeding Activity Alone Does Not Predict Regions of Neurodegeneration. PLoS Biol 14:e1002579
Saijo, Eri; Hughson, Andrew G; Raymond, Gregory J et al. (2016) PrPSc-Specific Antibody Reveals C-Terminal Conformational Differences between Prion Strains. J Virol 90:4905-13
Kraus, Allison; Anson, Kelsie J; Raymond, Lynne D et al. (2015) Prion Protein Prolines 102 and 105 and the Surrounding Lysine Cluster Impede Amyloid Formation. J Biol Chem 290:21510-22
Groveman, Bradley R; Kraus, Allison; Raymond, Lynne D et al. (2015) Charge neutralization of the central lysine cluster in prion protein (PrP) promotes PrP(Sc)-like folding of recombinant PrP amyloids. J Biol Chem 290:1119-28

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