Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy.
Inhibition of cerebral amyloid beta-protein deposition seems to be an important target for Alzheimer's disease therapy. Amyloidogenesis could be inhibited by short synthetic peptides designed as beta-sheet breakers. Here we demonstrate a 5-residue peptide that inhibits amyloid beta-protein fibrillogenesis, disassembles preformed fibrils in vitro and prevents neuronal death induced by fibrils in cell culture. In addition, the beta-sheet breaker peptide significantly reduces amyloid beta-protein 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.
Soto
C
C
Department of Pathology, New York University Medical Center, New York 10016, USA. Claudio.Soto@mcfpo.med.nyu.edu
Sigurdsson
E M
EM
Morelli
L
L
Kumar
R A
RA
Castaño
E M
EM
Frangione
B
B
D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D000686:Amyloidosis / Q000517:prevention & control*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)