# Cell Senescence and Death in Neurodegenerative Diseases

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $426,250

## Abstract

Project Summary/Abstract (30 lines)
Regardless of family history, site of onset, and sequence of symptoms and progression, all Amyotrophic Lateral
Sclerosis (ALS) patients lose muscle mass as the cells (motor neurons; MNs) that connect to muscle in limbs to control
movement stop working and eventually die. However, the complexity of the structure and function of the nervous
system is achieved through extensive developmental processes and is maintained in part due to the resiliency of the
cells to maintain function and resist activating cell death processes. Therefore, there appears to be an extensive
delay between initial neuronal dysfunction and physical degeneration. Experiments in this proposal will investigate a
novel hypothesis: motoneurons in ALS enter cellular senescence following neuromuscular (NMJ) denervation as part
of a complicated stress response to avoid active degeneration and cell death. Nonetheless, while this protective
mechanism may preserve the physical presence of the cell, senescent cell dysfunction and potentially toxic
secretome promotes chronic tissue degeneration over time that facilitates disease progression. We will further
investigate if pharmacological administration of well-characterized senolytics can effectively clear senescent
motoneurons and reduced neurotoxicity in the SOD1 mouse model of ALS. Successful outcome of these experiments
will open a novel avenue of investigation in ALS and develop new therapeutic targets. An area desperately in need of
development for the majority of ALS patients that die on average 2-4 years after diagnosis.

## Key facts

- **NIH application ID:** 10353662
- **Project number:** 1R21NS125171-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Carol Milligan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $426,250
- **Award type:** 1
- **Project period:** 2021-09-29 → 2025-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353662

## Citation

> US National Institutes of Health, RePORTER application 10353662, Cell Senescence and Death in Neurodegenerative Diseases (1R21NS125171-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10353662. Licensed CC0.

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