# Deciphering the Mechanisms and Cellular Roles of Monomer-Driven Actin Dynamics

> **NIH NIH R35** · AUGUSTA UNIVERSITY · 2024 · $331,342

## Abstract

Project Summary
There are currently no FDA-approved treatments for Alzheimer’s disease (AD) that target events that precede
the loss of synaptic connectivity and cognitive decline. The cytoskeleton of neurons plays a crucial role in the
development and maintenance of synaptic connections and dysregulation of the neuronal cytoskeleton is highly
implicated in Alzheimer’s disease (AD). However, the order of early pathological events that drive cytotoxicity
and neurodegeneration remain poorly understood. We recently discovered that depleting F-actin or inhibiting
nonmuscle myosin 2 in neuronal processes caused dramatic changes to the microtubule cytoskeleton and
dysregulated the transport of organelles in neuronal processes. This study revealed that disruption of actomyosin
can cause neurodegenerative disease-linked phenotypes which have not been attributed to the actin
cytoskeleton. Additionally, alterations to microtubules were completely reversed if actomyosin function was
restored, indicating that the actin cytoskeleton is potentially a target to control microtubule-based processes and
restore axonal defects. Based on our preliminary data, we hypothesize that dysregulation of actomyosin is an
early event in AD that primes axons for degeneration and modifying its activity can mitigate AD-related pathology.
The goal of this administrative supplement is to perform pilot studies to determine if neurons from Alzheimer’s
disease mouse models have actomyosin defects and if they appear in an age-dependent manner. We will also
modulate F-actin and myosin activity to investigate if the development of dystrophic neurites and axonal
fragmentation caused by the application of Aβ oligomers can be reduced. This project, which is a natural
extension of current work in the lab, will create a better understanding of the cellular events that cause AD and
potentially identify new targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 10940324
- **Project number:** 3R35GM137959-06S2
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Eric A Vitriol
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $331,342
- **Award type:** 3
- **Project period:** 2020-08-12 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940324

## Citation

> US National Institutes of Health, RePORTER application 10940324, Deciphering the Mechanisms and Cellular Roles of Monomer-Driven Actin Dynamics (3R35GM137959-06S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10940324. Licensed CC0.

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