Abstract

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. This fiscal year, we have extended studies of the influence of chaperone proteins and peptides on PrPres formation. One chaperone protein was found to act as an inhibitor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001087-03
Application #
8336297
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2011
Total Cost
$368,950
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
Ferreira, Natalia C; Marques, Icaro A; Conceição, Wesley A et al. (2014) Anti-prion activity of a panel of aromatic chemical compounds: in vitro and in silico approaches. PLoS One 9:e84531
Vieira, Tuane C R G; Cordeiro, Yraima; Caughey, Byron et al. (2014) Heparin binding confers prion stability and impairs its aggregation. FASEB J 28:2667-76
Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681
Hopping, Gene; Kellock, Jackson; Caughey, Byron et al. (2013) Designed Trpzip-3 ?-Hairpin Inhibits Amyloid Formation in Two Different Amyloid Systems. ACS Med Chem Lett 4:824-8
Wolfe, Lisa L; Kocisko, David A; Caughey, Byron et al. (2012) Assessment of prospective preventive therapies for chronic wasting disease in mule deer. J Wildl Dis 48:530-3
Taubner, Lara M; Bienkiewicz, Ewa A; Copié, Valérie et al. (2010) Structure of the flexible amino-terminal domain of prion protein bound to a sulfated glycan. J Mol Biol 395:475-90
Sim, Valerie L; Caughey, Byron (2009) Recent advances in prion chemotherapeutics. Infect Disord Drug Targets 9:81-91