# A chemical biology approach to studying the role of SARM1 in a novel degradative pathway

> **NIH NIH F31** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $18,629

## Abstract

Project Summary
The novel NAD glycohydrolase, SARM1, is an active executioner in progressive axonal and neuronal
degeneration1. This type of degeneration, termed Wallerian degeneration, defines a number of diseases,
including neuropathies, traumatic brain injury and neurodegenerative diseases, yet no therapies exist. In fact,
prior to the discovery of SARM1’s role in triggering Wallerian degeneration, the process was believed to occur
passively.
SARM1’s causal role in Wallerian degeneration demonstrates that it is an attractive therapeutic target that could
prevent disease progression. However, the design of therapeutics targeting SARM1 is limited by the dearth of
knowledge surrounding its inherent NADase activity. In order to evaluate SARM1’s therapeutic efficacy and
design potential SARM1 inhibitors, the proposed research will study its structure, enzymatic mechanism and
cellular activity. Solving the structure by leveraging the benefits of crystallography and cryoEM, determining the
enzymatic mechanism via a series of assays and analyzing the in vivo activity with activity-based probes will fill
in important gaps. Revealing these properties would enable the design of SARM1 inhibitors that could ultimately
treat Wallerian-type diseases. Moreover, demystifying the role SARM1 plays in neurodegeneration would also
allow for a better understanding of these disease types, the enzymatic capabilities of toll/interleukin receptor
(TIR) domains and the involvement of NADases in numerous disease states.

## Key facts

- **NIH application ID:** 9924674
- **Project number:** 5F31NS108610-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Heather Starr Loring
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $18,629
- **Award type:** 5
- **Project period:** 2018-06-25 → 2021-01-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924674

## Citation

> US National Institutes of Health, RePORTER application 9924674, A chemical biology approach to studying the role of SARM1 in a novel degradative pathway (5F31NS108610-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9924674. Licensed CC0.

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