Small molecules that boost the 20S proteasome to fight Alzheimer’s and related dementias
Official title: Small molecule induced degradation of intrinsically disordered proteins
Funded at University of Virginia · NIH-11606497 · Data updated 2026-11-12
A new approach tests small molecules that activate the 20S proteasome to help neurons clear harmful proteins and slow the spread of disease in people affected by Alzheimer's and related dementias.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Virginia NIH-funded |
| Lab location | 1 site (Charlottesville, United States) |
| Project start | September 10, 2026 |
| Project end | August 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $500,743 |
| NIH project number | 1R56AG092803-01A1 |
| Project ID | NIH-11606497 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with Alzheimer’s disease or related dementias who could benefit from therapies that enhance proteostasis and reduce brain pathology.
✕Less likely to help
Patients without proteostasis impairment or those not suited for small-molecule therapies may not benefit.
What this research studies
This grant explores how boosting the 20S proteasome could prevent protein clumps inside neurons and stop the spread of disease between cells. Researchers will identify two different chemical classes that activate the 20S proteasome and study how they work at the molecular level. The work aims to translate these findings into therapies that protect brain cells and slow dementia progression. The project centers on real disease biology with an emphasis on proteins that misfold and propagate pathology in Alzheimer’s and ADRD.
Why it matters
Potential benefit: If successful, this approach could lead to new treatments that reduce protein aggregation and transmission in Alzheimer’s disease and related dementias.
How similar studies have gone: Previous research shows proteostasis pathways are promising targets, but activating the 20S proteasome as a therapy is an emerging approach.
Where this research is happening
-
University of Virginia
Charlottesville, United States Active
Researchers
- Principal investigator: Tepe, Jetze J. — University of Virginia
- Study coordinator: Tepe, Jetze J.
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.