C. Soto et al., INHIBITION OF ALZHEIMERS AMYLOIDOSIS BY PEPTIDES THAT PREVENT BETA-SHEET CONFORMATION, Biochemical and biophysical research communications, 226(3), 1996, pp. 672-680
Amyloid beta-peptide (A beta) is a major fibrillar component of neurit
ic plaques in Alzheimer's disease (AD) brains and is related to the pa
thogenesis of the disease. We hypothesized that amyloid formation coul
d be inhibited by peptides homologous to A beta (position 17-21) with
a similar degree of hydrophobicity, but with a very low propensity to
adopt a beta-sheet conformation by incorporating proline residues (ant
i-beta-sheet peptides or beta-sheet inhibitors). An 11-residue peptide
with these characteristics binds to A beta, inhibits A beta fibril fo
rmation and partially disaggregates preformed fibrils in vitro. Shorte
r anti-beta-sheet peptides and analogs containing D-amino acids are al
so able to inhibit A beta fibrillogenesis. The latter are more resista
nt to proteolytic degradation and may serve as a starting point to des
ign more efficient peptides derivatives to inhibit amyloidogenesis in
vivo. (C) 1996 Academic Press, Inc.