INHIBITORS OF NEURITE GROWTH

The currently known inhibitory effects on neurite growth reviewed here fall into three groups: inhibitory effects exerted by defined molecules (membrane proteins neurotransmitters); molecules that are multifunctional in vitro (tenascin, J1-160/180): and descriptive evidence in several systems, which suggests the presence of additional inhibitory or repulsive molecules. In some of the latter examples, correlations exist with the specific localization of ECM components, in particular tenascin and sulfated proteoglycans. Unfortunately, experiments establishing a direct causal link between the presence of these constituents and neurite growth inhibition are sparse or lacking. Because tenascin can exert neurite growth-promoting, as well as inhibitory, effects in vitro depending on its presence as substrate or in soluble form and probably also on the combination with other LCM molecules, the situation urgently requires experiments in vivo or organ culture using site-specific antibodies for the various functional domains of the tenascin molecule. A slightly different situation exists for proteoglycans, which are a heterogeneous group of molecules where both the sugar parts and the protein backbones can exert inhibitory or growth promoting effects in vitro. Here, a detailed analysis of the proteoglycans actually present at the sites of growth inhibition is needed, including a dissection of the functional domains of these molecules and experiments using activity-neutralizing antibodies in vitro and in vivo. Of particular importance is whether the effects of sulfated proteoglycans are mediated by the high density of negative charges and the peculiar 'mucose' substrate properties epresented by these molecules or whether specific molecular interactions, including neuronal receptors are involved.