Therapeutic Applications Targeting SARM1

1 . A method reducing axonal and/or synaptic degradation in a neuron, the method comprising:

selecting a neuron with or at risk for axonal and/or synaptic degradation; and

contacting the neuron with an effective amount of a composition that inhibits sterile α/Armadillo/Toll-Interleukin receptor homology domain protein (SARM) activity and/or expression for a time sufficient to inhibit SARM activity and/or expression, thereby reducing axonal and/or synaptic degradation in the neuron.

2 . A method for reducing axonal and/or synaptic degradation in a subject with or at risk for developing axonal and/or synaptic degradation, the method comprising:

selecting a subject with or at risk for developing axonal and/or synaptic degradation; and

treating the subject with an effective amount of a composition that inhibits SARM activity and/or expression for a time sufficient to inhibit SARM activity and/or expression, thereby reducing axonal and/or synaptic degradation in the subject.

3 . The method of claim 2 , wherein the subject has or is at risk of neurodegenerative disease.

4 . The method of claim 2 or 3 , wherein the axonal and/or synaptic degradation is in the central nervous system (CNS) and/or the peripheral nervous system (PNS).

5 . The method of claim 4 , wherein the axonal and/or synaptic degradation is in the PNS.

6 . The method of claim 5 , wherein the subject has diabetes.

7 . The method of claim 6 , wherein the subject has diabetic neuropathy.

8 . The method of claim 5 , wherein the subject is scheduled to receive chemotherapy.

9 . The method of claim 5 , wherein the subject is receiving chemotherapy or has received chemotherapy.

10 . A method for identifying a compound that inhibits SARM activity and/or expression, the method comprising:

providing SARM;

contacting the SARM with a test compound; and

determining whether the test compound interacts with or binds to SARM, wherein a test compound that interacts or binds with SARM is a candidate compound that inhibits SARM activity and/or expression.

11 . The method of claim 10 , wherein SARM and the test compound are contacted in silico.

12 . The method of claim 10 or 11 , wherein SARM and the test compound are contacted in vitro.

13 . The method of claim 10 , wherein determining whether the test compound interacts with or binds to SARM is performed directly.

14 . The method of claim 10 , wherein determining whether the test compound interacts with or binds to SARM is performed indirectly.

15 . A method for identifying a compound that inhibits SARM activity and/or expression, the method comprising:

providing a sample comprising SARM;

contacting the sample with a compound; and

measuring the transcriptional activity of SARM in the sample, wherein a decrease in the transcriptional activity of SARM in the sample in the presence of the compound indicates that the compound is a candidate compound that inhibits SARM activity and/or expression.

16 . A method for identifying a compound that inhibits SARM activity and/or expression, the method comprising:

contacting a neuron with the candidate compound of claim 10 or claim 15 ;

axotomizing the neuron; and

determining whether axonal and/or synaptic degradation is altered in the presence of the candidate compound relative to axonal degradation in the absence of the compound, wherein a decrease in axonal and/or synaptic degradation indicates that the candidate compound is a compound that inhibits SARM activity and/or expression.

17 . The method of claim 16 , further comprising:

obtaining the compound;

administering the compound to an animal model of neurodegenerative disease; and

assessing the degenerative disease in the animal in the presence of the compound, wherein a decrease in degenerative disease in the presence of the compound indicates that the compound inhibits SARM activity and/or expression.