Flexible regions of alpha-synuclein and how they shape harmful protein clumps
Intrinsically disordered domains of α-synuclein: effect of fibril formation and fibril polymorphs
Researchers are looking at whether floppy ends of alpha-synuclein change the shape and interactions of protein clumps that occur in Lewy body dementia and related Alzheimer's-type conditions.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Southern California NIH-funded |
| Lab location | 1 site (Los Angeles, UNITED STATES) |
| Project ID | NIH-11308327 on NIH RePORTER |
What this research studies
Scientists will map the flexible, disordered ends (intrinsically disordered regions, or IDRs) that sit on the surface of alpha-synuclein fibrils found in Lewy body dementia and related dementias. They will use high-resolution structural tools such as solid-state NMR and cryo-electron microscopy together with biochemical experiments to determine the shapes, movements, and binding behaviors of these regions. Different fibril core shapes (polymorphs) will be compared to see how the ordered core influences the flexible tails and their interactions with proteins like DNAJB1. The team aims to build complete molecular models that include these flexible parts to better understand how fibrils may cause cell damage.
Who could benefit from this research
Good fit: People diagnosed with Lewy body dementia, Parkinson's disease with dementia, or other synucleinopathies who are willing to donate biological samples or enroll in future related studies would be most relevant.
Not a fit: Individuals whose dementia is not linked to alpha-synuclein pathology or who are unable or unwilling to provide samples are unlikely to receive direct benefit from this laboratory-focused research.
Why it matters
Potential benefit: If successful, this work could point to new targets or diagnostics to detect or block toxic alpha-synuclein clumps in Lewy body dementia and related disorders.
How similar studies have performed: High-resolution methods have successfully solved the ordered cores of many amyloid fibrils, but applying those approaches to the flexible IDRs on fibril surfaces is relatively new and less explored.
Where this research is happening
Los Angeles, UNITED STATES
- University of Southern California — Los Angeles, United States (Active)
Researchers
- Principal investigator: Siemer, Ansgar B — University of Southern California
- Study coordinator: Siemer, Ansgar B
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.