# Defining proteostasis networks in axon segments

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $361,780

## Abstract

PROJECT SUMMARY/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. In the aging
nervous system there is a well-documented decline in protein homeostasis and accumulation of protein
aggregates that threaten neuronal function. Protein homeostasis is predominantly studied in context of the
neuronal cell body. However, axons are also susceptible because protein aggregates interfere with transport
and disrupt synaptic function. Polypeptides are most vulnerable to misfolding and aggregation as they exit the
ribosome. Axons locally synthesize many proteins needed for survival however there is a gap in knowledge
regarding basic mechanisms that protect axons from protein misfolding. This project will determine the capacity
of axon segments to resist protein misfolding and aggregation. We will also determine the preferred
mechanisms used within axon segments for degrading non-native polypeptides and disposing of aggregates.
NAD+ levels decline as we age and this project will identify the consequences local NAD+ depletion on protein
homeostasis within the axon compartment. Altogether, this project will generate new insight on local
mechanisms controlling axon health and reveal treatment opportunities in neurodegenerative disorders.

## Key facts

- **NIH application ID:** 10829418
- **Project number:** 5R01NS127781-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Daniel Summers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $361,780
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829418

## Citation

> US National Institutes of Health, RePORTER application 10829418, Defining proteostasis networks in axon segments (5R01NS127781-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829418. Licensed CC0.

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