p75NTR antagonistic cyclic peptide decreases the size of beta amyloid-induced brain inflammation

Abstract

Amyloid beta (Abeta) was shown to bind the 75 kD neurotrophin receptor (p75(NTR)) to induce neuronal death. We synthesized a p75(NTR) antagonistic peptide (CATDIKGAEC) that contains the KGA motif that is present in the toxic part of Abeta and closely resembles the binding site of NGF for p75(NTR). In vivo injections of Abeta into the cerebral cortex of B57BL/6 mice together with the peptide produced significantly less inflammation than simultaneous injections of Abeta and a control (CKETIADGAC, scrambled) peptide injected into the contralateral cortex. These data suggest that blocking the binding of Abeta to p75(NTR) may reduce neuronal loss in Alzheimer's disease.

Fig. 1

p75^NTR antagonistic cyclic peptide decreases the size of Aβ-induced brain inflammation. About 14–16-week-old C57BL/6 mice were injected with Aβ and diluent (a) or Aβ and p75^NTR antagonistic cyclic peptide (b). Representative sections of the cerebral cortex stained with CV show that the inflammatory infiltrate, apparent along the injection track, is more extensive and more intense in (a) than in (b) (original magnification ×100). (c) C57BL/6 mice were injected with Aβ and p75^NTR antagonistic cyclic peptide or Aβ and scrambled peptide. Graphic representation of lesion size averaged over all mice. There is a statistically significant difference in lesion size between the hemispheres injected with Aβ and scrambled (control) peptide versus Aβ and p75^NTR antagonistic (active) peptide (P < 0.025). Mean ± SEM are displayed