How TDP-43 protein clumps damage brain cells by disrupting RNA processing
Determine the neurotoxicity of RNA metabolism dysfunction caused by cytoplasmic TDP-43 aggregates
Looks at whether clumps of the protein TDP-43 harm nerve cells by upsetting tiny RNA-processing bodies in people with Alzheimer’s, ALS, and related dementias.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Ut Southwestern Medical Center NIH-funded |
| Lab location | 1 site (Dallas, United States) |
| Project ID | NIH-11171644 on NIH RePORTER |
What this research studies
This project aims to find out how clumps of the protein TDP-43 change tiny RNA-processing structures (called P-bodies) inside neurons and lead to cell damage. Researchers will use high-resolution imaging, protein analysis (proteomics), and RNA sequencing to identify which proteins and RNAs are in P-bodies and how that mix shifts when TDP-43 aggregates form. They will study these changes in laboratory models and compare them with human tissue from people with ALS and Alzheimer’s-related dementia. The team hopes to link those molecular changes to how neurons stop working so we can point toward new ways to protect them.
Who could benefit from this research
Good fit: People with Alzheimer’s disease, limbic‑predominant TDP-43 encephalopathy (LATE), frontotemporal dementia, or ALS, and those willing to donate brain or spinal cord tissue for research, would be most relevant to this project.
Not a fit: Healthy people without neurodegenerative disease and those seeking an experimental treatment are unlikely to receive direct benefit from this laboratory-focused research.
Why it matters
Potential benefit: If successful, this work could reveal key steps that cause neuron damage and point to new targets to slow or prevent cognitive and motor decline in Alzheimer’s, ALS, and related dementias.
How similar studies have performed: Previous work has shown TDP-43 aggregates associate with RNA granules in many neurodegenerative diseases, but mapping P-body composition in vivo with combined imaging, proteomics, and sequencing is a relatively new approach.
Where this research is happening
Dallas, United States
- Ut Southwestern Medical Center — Dallas, United States (Active)
Researchers
- Principal investigator: Shahmoradian, Sarah H — Ut Southwestern Medical Center
- Study coordinator: Shahmoradian, Sarah H
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.