BETA-SHEET BREAKER PEPTIDES INHIBIT FIBRILLOGENESIS IN A RAT-BRAIN MODEL OF AMYLOIDOSIS - IMPLICATIONS FOR ALZHEIMERS THERAPY

Inhibition of cerebral amyloid beta-protein deposition seems to be an important target for Alzheimer's disease therapy. Amyloidogenesis coul d be inhibited by short synthetic peptides designed as beta-sheet brea kers. Here we demonstrate a 5-residue peptide that inhibits amyloid be ta-protein fibrillogenesis, disassembles preformed fibrils in vitro an d prevents neuronal death induced by fibrils in cell culture. In addit ion, the beta-sheet breaker peptide significantly reduces amyloid beta -protein deposition in vivo and completely blocks the formation of amy loid fibrils in a rat brain model of amyloidosis. These findings may p rovide the basis for a new therapeutic approach to prevent amyloidosis in Alzheimer's disease.