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β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Implications for Alzheimer's therapy

Abstract

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

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Soto, C., Sigurdsson, E., Morelli, L. et al. β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Implications for Alzheimer's therapy. Nat Med 4, 822–826 (1998). https://doi.org/10.1038/nm0798-822

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