Targeting ATase1 and ATase2 to fix ER protein-folding problems linked to autism
ATase1 and ATase2, proteostasis, and neurological diseases
This project tests drugs that target two enzymes (ATase1 and ATase2) to correct protein-folding problems that may contribute to autism and other neurological conditions.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Wisconsin-Madison NIH-funded |
| Lab location | 1 site (Madison, United States) |
| Project ID | NIH-11260278 on NIH RePORTER |
What this research studies
Researchers discovered a cell process in the endoplasmic reticulum (ER) controlled by AT-1, ATase1, and ATase2 that helps proteins fold properly and communicate between cell compartments. Genetic changes that disrupt this ER acetylation machinery have been linked to autism, intellectual disability, neuropathy, and other neurological problems. In mice that mimic those genetic changes, compounds targeting ATase enzymes restored normal protein handling and improved disease features. This program continues that work to understand how ATases cause disease and to develop treatments that could move toward testing in people.
Who could benefit from this research
Good fit: Ideal candidates would be people with autism spectrum disorder or related neurodevelopmental conditions who have known genetic changes affecting ER acetylation genes (for example SLC33A1/AT-1 or ATase-related genes).
Not a fit: People whose autism is unrelated to ER acetylation genetics, or those needing immediate clinical care, are unlikely to see direct benefit in the near term.
Why it matters
Potential benefit: If successful, this work could lead to new therapies that correct ER protein-folding defects and improve symptoms for people with autism related to these genetic changes.
How similar studies have performed: Preclinical studies in mouse models have shown that ATase-targeting compounds can rescue disease-related changes, but these approaches have not yet been proven safe or effective in humans.
Where this research is happening
Madison, United States
- University of Wisconsin-Madison — Madison, United States (Active)
Researchers
- Principal investigator: Puglielli, Luigi — University of Wisconsin-Madison
- Study coordinator: Puglielli, Luigi
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.