The transmissible spongiform encephalopathies (TSEs or prion diseases)are fatal untreatable neurodegenerative diseases such as scrapie, Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy and chronic wasting disease (CWD). TSE pathogenesis involves the accumulation of an abnormal misfolded protein, called PrPres, in infected hosts. In FY 2013: 1) We have collaborated with extramural investigators to identify a designed Trpzip-3 β-hairpin that inhibits amyloid formation in two different amyloid systems. 2) We have continued to search for new anti-prion compounds from libraries of novel compounds that have been synthesized in Brazil by our collaborators. A number of new compounds have been identified that block PrP-res formation and have other attractive characteristics, but further testing of these compounds will be required to better establish their therapeutic potential.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2013
Total Cost
$131,208
Indirect Cost
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Ferreira, N C; Ascari, L M; Hughson, A G et al. (2018) A Promising Antiprion Trimethoxychalcone Binds to the Globular Domain of the Cellular Prion Protein and Changes Its Cellular Location. Antimicrob Agents Chemother 62:
Kellock, Jackson; Hopping, Gene; Caughey, Byron et al. (2016) Peptides Composed of Alternating L- and D-Amino Acids Inhibit Amyloidogenesis in Three Distinct Amyloid Systems Independent of Sequence. J Mol Biol 428:2317-2328
Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681
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