An antineuronal monoclonal antibody that reverses neurite growth inhibition by central nervous system myelin

Abstract

A component of adult mammalian central nervous system (CNS) myelin causes collapse of neuronal growth cones and inhibits axonal growth, properties that may be responsible for the lack of regrowth of injured axons in the CNS. The molecules and detailed mechanism through which the inhibitory activity acts are not known. To study the cellular molecules mediating the response to this inhibitor, we have used an in vitro neurite growth inhibition assay to screen a panel of monoclonal antibodies raised against rat neuronal membrane proteins, for clones capable of blocking the response. One monoclonal antibody (10D) neutralized the inhibition of neurite growth seen when primary sympathetic neurons, PC12 cells or NG108-15 cells were grown on inhibitory CNS myelin substrates, but did not promote growth on non-inhibitory substrates. 10D reacted with neuronal cells but not myelin substrate proteins. The antigen recognized by 10D appears to play a role in the interaction between neurons and their growth substrates, and is a novel candidate for a cellular receptor or associated signalling molecule mediating the response to myelin inhibitors.