Cholesterol secosterol adduction inhibits the misfolding of a mutant prion protein fragment that induces neurodegeneration

Angew Chem Int Ed Engl. 2009;48(50):9469-72. doi: 10.1002/anie.200904524.

Abstract

Cholesterol secosterol aldehydes inhibit the misfolding of a prion protein fragment that induces GSS in mice. Atheronal-B completely inhibits the α to β-form transformation of MoPrP(89-143, P101L) via a mechanism that involves adduction to the protein. This result offers a paradigm shift in lipid aldehyde induced protein misfolding and offers a new molecular scaffold on which to develop new potential prion disease therapeutics

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / pharmacology
  • Animals
  • Cholesterol / analogs & derivatives*
  • Cholesterol / pharmacology
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mutant Proteins / pharmacology*
  • Neurodegenerative Diseases / etiology*
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology*
  • Prions / genetics
  • Prions / pharmacology*
  • Protein Conformation
  • Protein Folding / drug effects*
  • Protein Multimerization

Substances

  • Aldehydes
  • Mutant Proteins
  • Peptide Fragments
  • Prions
  • atheronal-B
  • Cholesterol