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

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.