# Anastasis in age-related neurodegeneration

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $223,750

## Abstract

Age-dependent neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and a variety
of less common disorders, affect large numbers of individuals and are largely untreatable. Novel mechanisms of
disease represent untapped potential for therapy development. Here we propose that anastasis (from the Greek,
“rising from the dead”), or recovery from terminal caspase activation, represents a new mechanism inducing
neuronal death in age-dependent neurodegenerative diseases. We present preliminary data derived from
models of Alexander disease, an exemplar primary astrocyte mediated neurodegenerative disorder, to suggest
that that anastasis drives neuronal death. We further capitalize on a valuable genome-scale genetic screen
performed in an in vivo Drosophila model of Alexander disease to define mechanisms controlling glial anastasis
and secondary non-cell autonomous neurodegeneration. We then test the hypothesis that anastasis contributes
to neurodegeneration in Drosophila models of relevant to Alzheimer’s disease and related disorders. Finally, we
examine mouse models of tauopathy for markers associated with anastasis. Our studies have the potential to
define a new mechanism mediating neurodegeneration in aging-related disorders with accompanying
opportunities for development of approaches to slow the onset and progression of neurological decline.

## Key facts

- **NIH application ID:** 10746840
- **Project number:** 5R21AG080713-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MEL B FEANY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $223,750
- **Award type:** 5
- **Project period:** 2022-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746840

## Citation

> US National Institutes of Health, RePORTER application 10746840, Anastasis in age-related neurodegeneration (5R21AG080713-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10746840. Licensed CC0.

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