INABILITY OF BETA-AMYLOID (25-35) TO BIND TO CENTRAL-NERVOUS-SYSTEM NEUROKININ-1 RECEPTORS

Beta-amyloid (1-40) has recently been shown to exhibit both neurotoxic and neurotrophic properties. The putatively active moiety is beta-(25-35), which has a structural homology to the human tachykinin substance P. Substance P, which preferentially binds to neurokinin 1 (NK1) receptors in the central nervous system (CNS), has been shown to block the neurotoxic effects of beta-amyloid (1-40). These data suggest that effects of beta-amyloid may be mediated by an NK1 receptor-mediated process. However, in the present study, we demonstrate that beta-(25-35) is unable to competitively inhibit the binding of 0.15 nM I-125-substance P from rat CNS NK1 receptors. Therefore, the mechanisms of action of beta-amyloid neurotoxic effects are probably not to be mediated through a NK1 receptor-mediated process.