# A Precision high content screening assay for AB-mediated neuronal cell cycle reentry

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $403,750

## Abstract

Project Summary
The death of neurons that control memory and cognition are responsible for the behavioral symptoms of
Alzheimer’s disease (AD). One of the most common pathways for neuronal death in AD is cell cycle re-entry
(CCR), which represents the reactivation of neuronal cell cycle machinery. Usually, differentiated neurons
never attempt to divide, yet up to 5-10% of the neurons in brain regions affected by AD show signs of CCR.
These neurons, which typically have duplicated much of their DNA, fail to undergo cytokinesis. Instead, they
eventually die and may account for as much as 90% of the neuronal loss seen in AD. This process initiates
with exposure to soluble amyloid-β oligomers (AβOs), which are the building blocks of the insoluble amyloid
plaques that accumulate in AD brain. Identifying genes and proteins that mediate AβO-mediated neuronal CCR
and defining relevant signaling networks hold promise for early AD diagnosis and for developing new AD
therapeutics. We have developed a human neural cell model of AβO-mediated neuronal CCR, which utilizes
neural iPS cell lines. We intend to use these iPS lines and derived sublines to develop a high content
screening (HCS) assay to identify chemotypes that inhibit AβO-mediated CCR. We believe, through this assay,
we can identify small molecules that can block AβO-induced neuronal CCR and function as chemical probes to
(1) understand the signaling pathways leading to neuronal death by CCR and (2) serve as parental
chemotypes for drugs.

## Key facts

- **NIH application ID:** 10137862
- **Project number:** 5R01AG063400-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** ELIZABETH SHARLOW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137862

## Citation

> US National Institutes of Health, RePORTER application 10137862, A Precision high content screening assay for AB-mediated neuronal cell cycle reentry (5R01AG063400-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137862. Licensed CC0.

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