Functional inhibition of the p75 receptor using a small interfering RNA

Abstract

The neurotrophin receptor p75 NTR mediates a wide variety of biological effects. Consistent with the function in controlling the survival and neurite formation, p75 NTR is expressed during the developmental stages of the nervous system. Importantly, p75 NTR is re-expressed in various pathological conditions and is suggested to contribute to the inhibition of neuronal regeneration and the death of the neurons. Here we develop a tool to knock down the expression of p75 NTR by employing a small interfering RNA (siRNA). The siRNA for p75 NTR effectively reduces the expression of endogenous p75 NTR both in Schwann cells and dorsal root ganglion neurons in vitro. NGF-induced cell death in Schwann cells and the neurite retraction in DRG neurons induced by myelin-associated glycoprotein are attenuated by the siRNA. Inhibition of p75 NTR in specific pathological conditions by the siRNA may provide a potential therapeutic agent.