Mutant huntingtin-mediated protein dysfunction
The present invention relates to methods of inhibiting neurodegeneration in a subject suffering from or genetically at risk and/or destined to develop Huntington's Disease comprising increasing, in neurons of the subject, the activity of the TIM23 mitochondrial protein import complex.
1. A method of decreasing an interaction between a mutant Huntingtin protein and a TIM23 complex in a subject having a Huntington's Disease, comprising administering to the subject an effective amount of an agent that comprises:
(a) an exogenous TIM23 complex protein consisting essentially of subunits Tim23, Tim50, and Tim17a; or
b) a nucleic acid molecule encoding the subunits Tim23, Tim50, and Tim17a.
2. The method of claim 1 , wherein the mutant Htt protein comprises at least 35 glutamine repeats (35Q).
3. The method of claim 1 , wherein the nucleic acid molecule is operably linked to a promoter that is constitutively active or inducible in the subject.
4. The method of claim 1 , wherein the nucleic acid molecule is administered to the subject via a vector.
5. A method of decreasing an interaction between a mutant Huntingtin protein and a TIM23 complex in a neuron, comprising
(a) contacting the neuron with an effective amount of an exogenous TIM23 complex protein that consists essentially of subunits Tim23, Tim50, and Tim17a; or
(b) introducing into the neuron a nucleic acid molecule encoding the subunits Tim23, Tim50, and Tim17a.
6. The method of claim 5 , wherein the nucleic acid molecule is operably linked to a promoter that is constitutively active or inducible in the neuron.
7. The method of claim 5 , wherein the nucleic acid molecule is introduced into the neuron via a vector.