Cylindrins as etiologic agents of amyloid diseases

Abstract

This invention relates, e.g., to a cylindrin, which is a non-covalent assembly of substantially identical chains of an amyloid or amyloid-related protein, which is a non-covalent assembly of substantially identical chains of an amyloid or amyloid-related protein, wherein each chain has a length of about 10-100 amino acid residues and comprises a single copy of a cylindrin-forming segment, or tandem adjacent copies of a cylindrin-forming segment, optionally separated by spacers, or adjacent copies of a first cylindrin-forming segment and a second complementary segment of the first cylindrin-forming segment, optionally separated by spacers, wherein at least about ⅔ of the amino acid residues in the chain are cylindrin-forming segments, wherein the cylindrin is a curved beta sheet formed from anti-parallel out-of-register extended protein strands, which is substantially filled with packed side chains. Also disclosed are methods for designing and making cylindrins, and methods for using them to identify inhibitors cylindrin-mediated cell toxicity.

Dependencies are inferred from the claim text.