# Defining the Role of Lactate in Axon Degeneration

> **NIH NIH F31** · YALE UNIVERSITY · 2023 · $32,612

## Abstract

Project Summary/Abstract
Axon degeneration is a conserved and tightly regulated process and is a driving force of later pathologies in
many neurodegenerative diseases. There is a lack of treatments for neurodegeneration that results from
disease, and axon degeneration is a target for early intervention and prevention. Elucidating the specific
mechanisms that initiate axon degeneration could assist in identifying ways to protect axons in disease and
ultimately treat neurodegeneration.
C. elegans Mitochondrial Trafficking Mutants (MTMs) have no axonal mitochondria, resulting in axon
degeneration. In preliminary experiments the applicant made a surprising discovery: inhibiting glycolysis in
MTMs suppresses axon degeneration. Following this finding the applicant showed that degrading the enzyme
responsible for lactate production rescues degeneration of axons, suggesting that lactate accumulation may
drive axon degeneration. However, the molecular mechanism by which this occurs is unknown. This
observation prompted the hypothesis that the product of glycolysis, lactate, accumulates in the absence of
mitochondria and by creating a more acidic axonal environment instigates degeneration.
Completion of this proposed work will elucidate the role of lactate and related metabolites on axon
degeneration (Aim 1). Further, it will shed light on the consequences of loss of axonal mitochondria for
neurons —a key feature of neurodegenerative diseases. Finally, these experiments may identify novel
approaches for preventing morphological and functional axon degeneration (Aim 2).
Work proposed here will establish the role of lactate in axon degeneration and further our understanding of the
coupling between neuronal activity and lactate in health and disease.
Upon completion of this fellowship the trainee will have received extensive training in an environment well
equipped to support collaborative and cutting-edge research. The trainee will gain technical and analytical
skills, and professional independence in preparation for an academic career in cellular and molecular
neuroscience.

## Key facts

- **NIH application ID:** 10750375
- **Project number:** 1F31NS134151-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Hadas Tal
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $32,612
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750375

## Citation

> US National Institutes of Health, RePORTER application 10750375, Defining the Role of Lactate in Axon Degeneration (1F31NS134151-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10750375. Licensed CC0.

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