INHIBITORS AND DISASSEMBLERS OF FIBRILLOGENESIS

摘要

Methods and compositions are presented that inhibit fibril formation and/or bring about disassembly of pre-formed fibrils. Compositions include peptides with short DOLLAR g(b)-strands with two faces : one that can bind to DOLLAR g(b)-amyloids through hydrogen bonds, and one which blocks propagation of hydrogen bonding needed to form fibrils. Thus, short congeners of the fibril protein containing N-methyl amino acids or esters are provided for the inhibition of fibril formation and for the disassembly of pre-existing or pre-formed fibrils. Specific aspects address DOLLAR g(b)-amyloid fibrils; prion mediated fibrils; Huntington protein fibrils. Methods for screening for potential fibril inhibitors and disassemblers, diagnostic analysis and treatments are provided.