How the AT‑1 protein and ER acetylation may link autism, spastic paraplegia, and nerve degeneration
Spastic paraplegia, neurodegeneration and autism: possible role for AT- 1/SLC33A1?
This project looks at whether problems with the AT‑1 protein and a cell process called ER acetylation contribute to autism, spastic paraplegia, and related neurodegeneration.
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-11290624 on NIH RePORTER |
What this research studies
Researchers aim to understand how AT‑1/SLC33A1 and two acetyltransferases control protein handling inside the cell's endoplasmic reticulum and how that may cause neurodevelopmental and neurodegenerative symptoms. They use biochemical methods and high‑definition mass spectrometry and have created 19 mouse models that replicate human mutations tied to epilepsy, developmental delay, neuropathy, and autism with intellectual disability. The team studies how citrate and acetate metabolic pathways influence AT‑1 activity and how changes affect quality control and reticulophagy in the secretory pathway. Results are intended to clarify disease mechanisms and point toward genetic markers or new treatment targets.
Who could benefit from this research
Good fit: People with autism spectrum disorder, spastic paraplegia, early-onset neurodegeneration, or known mutations in SLC33A1, SLC25A1, SLC13A5, ACSS2, or COASY would be most relevant to this work.
Not a fit: Patients whose condition is unrelated to ER acetylation pathways or who lack relevant genetic changes are unlikely to benefit directly from this project.
Why it matters
Potential benefit: If successful, this work could reveal biological targets and genetic markers that lead to new diagnostics or therapies for autism-related and neurodegenerative conditions.
How similar studies have performed: Laboratory studies have already discovered the ER acetylation machinery and validated disease links in mouse models, but direct patient treatments based on this approach remain untested.
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.