Reducing axon degeneration with proteasome inhibitors

1. A method of reducing degeneration of an axon predetermined to be subject to degenerative neuropathy in a term patient, the method comprising:

contacting the axon in situ with an effective amount of a ubiquitin-proteasome system (UPS) inhibitor sufficient to reduce degeneration of the axon; and

detecting a resultant reduction in the degeneration of the axon in situ,

wherein the inhibitor is a proteasome inhibitor selected from the group consisting of:

MG-132 (Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal),

MG-115 (Carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal),

PSI(Carbobenzoxy-L-isoleucyl-γ-t-butyl-L-glutamyl-L-alanyl-L-leucinal),

Lactacystin (Synthetic: N-Acetyl-L-Cysteine, S-[2R,3 S,4R]-3-Hydroxy-2-[(1S)-1-Hydroxy-2-Methylpropyl]-4-Methyl-5-Oxo-2-Pyrolidinecarbonyl]),

PS-519 (clasto-Lactacystin β-Lactone),

α-Methylomuralide(α-Methyl clasto-Lactacystin β-Lactone),

MG-101 (Ac-Leu-Leu-Nle-CHO),

MG-262 (Z-Leu-Leu-Leu-B(OH)2),

PS-341 (Velcade; bortezomib), and

Epoxomicin ((2R)-2-[Acetyl-(N-Methyl-L-Isoleucyl)-L-Isoleucyl-L-Threonyl-L-Leucyl]-2-Methyloxirane),

wherein the degenerative neuropathy is axon trauma or axotomy, and

wherein the contacting is effected by local, regionally-restricted delivery of the inhibitor proximate to the axon.

2. The method of claim 1 , wherein the delivery is effected with a slow release gel-foam or osmotic pump.

3. The method of claim 1 , wherein the contacting step avoids contact with the cell body of a neuron comprising the axon.

4. The method of claim 1 , wherein the degenerative neuropathy is in the absence of substantial neuro-necrosis.

5. The method of claim 1 , wherein the method consists essentially of the recited contacting and detecting steps.

6. The method of claim 1 , wherein the inhibitor is delivered in conjunction with a microtubule stabilizing reagent.

7. The method of claim 1 , wherein preceding the contacting step, the method comprises diagnosing the neuropathy.

8. The method of claim 1 , wherein the axon is a central nervous system (CNS) axon.

9. The method of claim 1 , wherein the axon is a peripheral nervous system (PNS) axon.

10. The method of claim 1 , wherein the inhibitor is MG-132.

11. The method of claim 1 , wherein the inhibitor is MG-115.

12. The method of claim 1 , wherein the inhibitor is PSI.

13. The method of claim 1 , wherein the inhibitor is Lactacystin.

14. The method of claim 1 , wherein the inhibitor is PS-519.

15. The method of claim 1 , wherein the inhibitor is α-Methylomuralide.

16. The method of claim 1 , wherein the inhibitor is MG-101.

17. The method of claim 1 , wherein the inhibitor is MG-262.

18. The method of claim 1 , wherein the inhibitor is PS-341.

19. The method of claim 1 , wherein the inhibitor is Epoxomicin.