Dna-damage-induced proteolysis

Abstract

The present application provides methods for identifying compounds for inhibiting DNA damage-induced Htt proteolysis, and methods and compositions for protecting cells from DNA damage-induced cleavage of Htt.

1 .- 24 . (canceled) 
     
     
         25 . A method for protecting at least one cell from DNA damage, comprising
 inhibiting DNA damage-induced Htt proteolysis in at least one cell by contacting said at least one cell with at least one compound selected from the group consisting of an IKKβ inhibitor, an IKKα activator, and a Bcl-xL inducer.   
     
     
         26 . The method of  claim 25 , wherein the at least one cell is a neuron. 
     
     
         27 . The method of  claim 25 , wherein the at least one compound is selected from the group consisting of a small molecule, a nucleic acid, a peptide, and an antibody. 
     
     
         28 . The method of  claim 25 , wherein the at least one compound is an IKKβ inhibitor. 
     
     
         29 . The method of  claim 28 , wherein the IKKβ inhibitor is selected from the group consisting of herbimycin, sodium salicylate, retinoid-related compounds, cyclopentenone prostaglandins, anti-IKKβ small hairpin RNA (shRNA), IKKα, tricyclic based inhibitors of IKK, and some combination thereof. 
     
     
         30 . The method of  claim 29 , wherein the tricyclic based inhibitors of IKK comprise oxazole-based IKK inhibitors, thiazole-based IKK inhibitors, and imidazole-based IKK inhibitors. 
     
     
         31 . The method of  claim 25 , wherein the at least one compound is an IKKαactivator. 
     
     
         32 . The method of  claim 31 , wherein the IKKα activator is selected from the group consisting of IGF, netrin, and some combination thereof. 
     
     
         33 . The method of  claim 25 , wherein the at least one compound is a Bcl-xL inducer. 
     
     
         34 . The method of  claim 33 , wherein the Bcl-xL inducer is selected from the group consisting of IKKα, green tea polyphenol (GTP), epigallocatechin gallate (EGCG), Bcl-xL, IGF, BDNF, cystamine, memantine, and some combination thereof. 
     
     
         35 . (canceled)