# Identifying mechanisms that regulate local axon vulnerability to pathological degeneration

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $373,732

## Abstract

Neurodegenerative disorders represent a significant challenge to human health. Many therapeutic strategies
revolve around suppressing death of the neuronal cell body. However, neuronal connectivity depends on long
projections called axons that use specialized mechanisms to survive in isolation from the soma. The
degeneration of axons is a common, sometimes initiating event in a variety of neurodegenerative disorders
including Alzheimer’s disease, Parkinson’s disease, and peripheral neuropathies. Protecting axon health is
necessary for sustaining functional connectivity and will have broad relevance to many diseases. Disease
onset and severity can vary significantly between patients suggesting there are important, undiscovered factors
that influence axon vulnerability to pathological degeneration. The goal of this project is to define novel
pathways controlling the fate of a damaged axon. Axon injury stimulates a local self-destruct mechanism that
promotes axon dismantling and clearance by the immune system. The enzymes NMNAT2 and SARM1
represent a critical regulatory node in this self-destruction program. Boosting NMNAT2 is neuroprotective and
has therapeutic potential. We will define a new mechanism controlling NMNAT2 abundance in axon segments.
We will also identify new contributions for autophagy in axon susceptibility and stress signaling. These studies
will generate new insight on local mechanisms controlling axon health and reveal new treatment opportunities
in neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10415770
- **Project number:** 1R01NS126191-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Daniel Summers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $373,732
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415770

## Citation

> US National Institutes of Health, RePORTER application 10415770, Identifying mechanisms that regulate local axon vulnerability to pathological degeneration (1R01NS126191-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10415770. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*