Modulation of axon degeneration

Abstract

The invention relates generally to treatment of neurological disorders and nervous system injuries. The invention specifically provides methods of using modulators of particular target proteins to modulate degeneration of neurons or portions thereof, such as axons.

What is claimed is: 
     
         1 . A method of identifying an agent for use in inhibiting degeneration of a neuron or portion thereof, the method comprising contacting a neuron or portion thereof with a candidate agent in an assay of axon or neuron degeneration, wherein detection of reduced degeneration of the neuron or portion thereof in the presence of the candidate agent, relative to a control, indicates the identification of an agent for use in inhibiting degeneration of a neuron or portion thereof. 
     
     
         2 . The method of  claim 1 , wherein the assay of axon or neuron degeneration is selected from the group consisting of anti-nerve growth factor (NGF) antibodies, serum deprivation/KCl reduction, and rotenone treatment. 
     
     
         3 . The method of  claim 1 , wherein the candidate agent is selected from the group consisting of an antibody, polypeptide, peptide, peptibody, nucleic acid molecule, short interfering RNA (siRNA), polynucleotide, aptamer, small molecule, and polysaccharide. 
     
     
         4 . A method for activating degeneration of a neuron or a portion thereof, the method comprising administering to a neuron or portion thereof an agent that modulates: (i) the activity or expression of a target protein in the neuron or portion thereof, or (ii) a process in the neuron or portion thereof. 
     
     
         5 . The method of  claim 4 , wherein the target protein is selected from the group consisting of dual leucine zipper-bearing kinase (DLK), glycogen synthase kinase 3β (GSK3β), p38 mitogen-activated protein kinase (p38 MAPK), epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 5 (cdk5), adenylyl cyclase, c-Jun N-terminal kinase (JNK), BCL2-associated X protein (Bax), Ih channel, calcium/calmodulin-dependent protein kinase kinase (CaMKK), a G-protein, a G-protein coupled receptor, transcription factor 4 (TCF4), and β-catenin; or
 the process is transcription or protein synthesis. 
 
     
     
         6 . The method of  claim 4 , wherein the agent is an activator of the target protein or process. 
     
     
         7 . The method of  claim 4 , wherein said modulation of a target protein is an increase in the activity or expression of GSK3β, a decrease in the activity or expression of β-catenin, and/or a decrease in the activity or expression of TCF4.