Axon loss is a recurrent feature in many prevalent neurological disorders, such as peripheral neuropathies, traumatic brain injury, Parkinson's disease, and glaucoma. At the heart of the process leading to axon loss is SARM1, the principal executor of the pathway responsible for axonal degeneration. After axonal injury SARM1's TIR domain initiates the degradation of NAD+, resulting in a type of axonal demise known as Wallerian degeneration. SARM1 is characterized by an N-terminal armadillo repeat (ARM) domain, which is followed by a tandem set of sterile alpha motif (SAM) domains, and a C-terminal toll/interleukin receptor (TIR) domain. The TIR domain possesses intrinsic nicotinamide adenine dinucleotide (NAD) hydrolase (NADase) activity. With catalytic cleavage executed by a conserved glutamic acid (E642) cleaving NAD+ into ADP Ribose (ADPR), cyclic ADPR, and Nicotinamide mononucleotide (NMN), NMN is a forward-feeding byproduct. Base exchange reactions between NAD+ and small molecules/fragments inhibit NMN byproduct formation. Observed through fluorescence assays, multiple fragment structures reduce fluorescence intensity signifying E642 binding and inhibition of active SARM1. Compounds shown to inhibit assembly formation will be characterized in more detail for protein interaction using Saturation Transfer Difference (STD) NMR, surface plasmon/isothermal titration calorimetry, and X-ray Crystallography. This information will then be used with molecular modeling and structure analysis to generate more effective small-molecule inhibitors as potential leads for drugs.