THY-1 RECEPTOR AND CNS NEURITE REGENERATION

如果中枢神经系统的神经细胞能够再生

If nerve cells in the central nervous system could regenerate their processes (axons and dendrites), it would become possible to treat injuries to these processes due, for example, to stroke. This proposal describes one class of substances that has recently been recognized to be important in regeneration in the mammalian central nervous system because of work in tissue culture and in vivo. Thy-1 is the most abundant glycoprotein in rat neurons; homologues have been identified in species from invertebrates to man. Specific Thy-1 antibodies have been shown to promote regeneration of processes (also termed neurites) by mammalian retinal ganglion cells. Thy-1 antibodies have, as well, promoted optic nerve growth after transection. The growth of other types of central neurons also appears to be influenced by these antibodies (nearly all neurons have Thy-1 glycoprotein on their surface membrane). It is therefore proposed that there exists a naturally occurring Thy-l-receptor that is analogous to the Thy-1 antibodies. This Thy-1-receptor may influence the outgrowth and regeneration of neuronal processes by central mammalian neurons, such as retinal ganglion cells, by binding to the Thy-1 molecule on the surface of neurons in the same way that the Thy-1 antibody does. The current grant proposes to purify an endogenous Thy-l-receptor by using as probes two monoclonal anti-idiotype antibodies against Thy-1 antibodies and a recently purified form of the Thy-1 molecule. The Thy-l-receptor has already been tentatively identified in preliminary experiments using immunofluorescence techniques, isoelectric focusing, and molecular biological approaches. The presence of a homologue of Thy-1 on human CNS neurons indicates that these studies may have relevance to the problem of CNS regeneration after stroke in man.