Jf. Flood et al., TOPOGRAPHY OF A BINDING-SITE FOR SMALL AMNESTIC PEPTIDES DEDUCED FROMSTRUCTURE-ACTIVITY STUDIES - RELATION TO AMNESTIC EFFECT OF AMYLOID BETA-PROTEIN, Proceedings of the National Academy of Sciences of the United Statesof America, 91(1), 1994, pp. 380-384
Four peptides homologous to amyloid beta protein containing the Val-Ph
e-Phe (VFF) sequence administered intracerebroventricularly after trai
ning caused amnesia for footshock active avoidance training in mice. R
esults with VFF and other peptides containing VFF or portions thereof
were used to generate a topographic map for a hypothetical binding sur
face for amnestic peptides, termed Z. Effects on retention of footshoc
k active avoidance training were rationalized in terms of fit to Z, ma
king possible design of potential memory-modulating peptidic and nonpe
ptidic substances. Three peptides that neither improved nor impaired r
etention blocked the amnestic effects of beta-(12-28), a peptide homol
ogous to amyloid beta protein, opening the way to development of subst
ances that can antagonize the neurotoxic effects of amyloid beta prote
in on neural structures and thus attenuate symptoms and progression of
Alzheimer disease.