Wallerian degeneration of the axon is central to many neurodegenerative diseases and axonal injuries. The axon degeneration pathway involves two regulatory enzymes: nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) and sterile alpha and toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1). Injury or disease causes a decrease in NMNAT2 levels, which leads to the activation of SARM1, a main contributor to axon degeneration. SARM1 catalyzes the hydrolysis of NAD+ to form nicotinamide (NAM), ADP ribose (ADPR), and cyclic ADPR (cADPR) in the NAD+ salvage pathway, but little is still known about the mechanism by which this catalysis happens. This study indicates that there may be another cellular component necessary for ADP ribosylation catalysis by SARM1. Additionally, mutations to the active site showed increased catalytic efficiency and ADP ribosylation, further indicating a link between this site and SARM1’s activity. Future studies on the effect of various mutations on the activity of SARM1 in different metabolite concentrations will help further the understanding of the mechanism and conditions by which SARM1 catalyzes NAD+ hydrolysis.

• This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

Creator

• Mastergeorge, Eliza

Publisher

• Worcester Polytechnic Institute

Identifier

• 106746
• E-project-042723-195505

Advisor

• Mattson, Anita Elaine

Year

• 2023

Date created

• 2023-04-27

Resource type

• Major Qualifying Project

Major

• Chemistry

Source

• E-project-042723-195505

Rights statement

• In Copyright

Last modified

• 2023-06-20