Turning on cells' cleanup system to help remove toxic tau in Alzheimer's
Mechanisms and therapeutic potential of the autophagy-lysosome pathway in Alzheimer’s disease
This project looks at whether activating a cell's waste-removal machinery can help clear harmful tau protein linked to Alzheimer's disease in older adults.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sloan-Kettering Inst Can Research NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11248807 on NIH RePORTER |
What this research studies
From a patient's point of view, researchers are focused on the cell's autophagy-lysosome system and its master regulator TFEB, which helps cells clear damaged proteins like tau. They are studying how two enzymes, CDC25A and ASAH1, influence TFEB through signaling partners (AMPK and PP2A) and how blocking those enzymes can switch TFEB on. The team will use lab-grown cells and Alzheimer's mouse models to test whether inhibiting CDC25A and ASAH1, alone or together, speeds removal of tau aggregates. The work aims to identify drug targets and combinations that could eventually be tested in people with Alzheimer's disease.
Who could benefit from this research
Good fit: Ideal candidates for future trials would be older adults (typically 65+) with Alzheimer's disease marked by tau pathology.
Not a fit: People without tau-driven Alzheimer's, those with other types of dementia, or individuals without significant brain tau pathology are unlikely to benefit directly from this approach.
Why it matters
Potential benefit: If successful, this work could point to new treatments that help clear tau protein and slow Alzheimer's progression.
How similar studies have performed: Previous animal studies showed TFEB activation can reduce Alzheimer's-like changes in mice, and the investigators' preliminary work found CDC25A and ASAH1 inhibition activates TFEB and promotes tau clearance in models, but human benefit is not yet proven.
Where this research is happening
New York, United States
- Sloan-Kettering Inst Can Research — New York, United States (Active)
Researchers
- Principal investigator: Li, Yueming — Sloan-Kettering Inst Can Research
- Study coordinator: Li, Yueming
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.