Methods of promoting CNS neuronal repair by inhibiting LRP-1
This invention provides methods for promoting and/or restoring neurite outgrowth and neuronal regeneration by contacting an injured neuron with an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1).
1. A method of enhancing nerve growth or neuronal regeneration, comprising contacting a neuron with an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1) activity in the presence of a myelin-associated inhibitory protein, wherein the inhibitor of LRP-1 activity is receptor associated protein (RAP).
2. The method of claim 1 , wherein the neuron is a central nervous system neuron.
3. The method of claim 1 , wherein the neuron is in vitro.
4. The method of claim 1 , wherein the neuron is in vivo.
5. The method of claim 1 , wherein the myelin-associated inhibitory protein is selected from the group consisting of myelin associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), Nogo-A, Nogo-B, Nogo-C, ephrin-B3, Sema4D/CD100, repulsive guidance molecule b, and fragments thereof.
6. The method of claim 1 , wherein the inhibitor of LRP-1 activity inhibits binding or endocytosis of myelin.
7. The method of claim 1 , wherein the inhibitor of LRP-1 activity inhibits myelin associated glycoprotein (MAG) activation of Rho or association with p75NTR.
8. The method of claim 1 , wherein the inhibitor of LRP-1 activity inhibits LRP-1 association with p75NTR.
9. A method of enhancing nerve growth or neuronal regeneration in a subject in need thereof, comprising administering to the subject an effective amount of an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1) activity, wherein the inhibitor of LRP-1 activity is receptor associated protein (RAP), and further wherein the subject is a human.
10. The method of claim 9 , wherein the subject has experienced an injury to the central nervous system.
11. The method of claim 10 , wherein the subject has experienced a spinal cord injury.
12. The method of claim 10 , wherein the subject has experienced a traumatic brain injury.
13. The method of claim 9 , wherein the inhibitor of LRP-1 activity inhibits binding or endocytosis of myelin.
14. The method of claim 9 , wherein the inhibitor of LRP-1 activity inhibits myelin associated glycoprotein (MAG) activation of Rho or association with p75NTR.
15. The method of claim 9 , wherein the inhibitor of LRP-1 activity inhibits LRP-1 association with p75NTR.
16. The method of claim 10 , wherein the inhibitor of LRP-1 activity is administered directly to the injury.