Cholesterol Secosterol Adduction Inhibits the Misfolding of a Mutant Prion Protein Fragment that Induces Neurodegeneration

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