# Determining the influence of cellular environments on a-synuclein fibril conformations

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $244,203

## Abstract

Neurodegeneration in Parkinson's disease (PD) is closely associated with the accumulation of α-
synuclein (α-syn) protein aggregates known as Lewy bodies. Understanding the diverse conformations
adopted by α-syn in both healthy and diseased states is crucial for developing effective interventions.
Recent advances in structural biology have provided valuable insights into the structural diversity of α-
syn amyloid fibrils. However, the extent to which these in vitro models represent the conformations
amplified in biological settings remains uncertain. This uncertainty hinders our ability to develop tools
like PET-tracers, small molecules that bind to amyloid fibrils that can be used to localize and monitor
disease progression in vivo. This project aims to bridge this gap by determining if the amyloid
conformations that can be propagated in vitro can be propagated inside cells. To do so, we will leverage
the sensitivity gains of dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR)
spectroscopy to investigate the conformations of α-syn fibrils amplified inside cells and compare them
with in vitro amplified fibrils. By using biosensor cell lines capable of propagating α-syn amyloid
conformations, we will examine the structural features of α-syn fibrils in cellular environments. This
knowledge will facilitate the optimization of in silico structure-based and chemical screens to identify
selective α-syn ligands.

## Key facts

- **NIH application ID:** 10869240
- **Project number:** 1R21NS136951-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Kendra King Frederick
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $244,203
- **Award type:** 1
- **Project period:** 2024-03-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869240

## Citation

> US National Institutes of Health, RePORTER application 10869240, Determining the influence of cellular environments on a-synuclein fibril conformations (1R21NS136951-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10869240. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*