Study Rationale:
Parkinson’s disease (PD) is the fastest-growing neurodegenerative disorder, yet we still don’t fully understand why brain cells become vulnerable and die. Recent work suggests that mistakes in how cells handle RNA — the molecule that helps turn genes into proteins — may drive this process. Proteins linked to PD, like alpha-synuclein, can stick to RNA-binding proteins and disrupt normal RNA processing, leading to cell stress and damage. Our team has also found that unusual fragments of RNA, called tRNA fragments (tRFs), may appear early in PD and could serve as important clues to what’s going wrong in the brain.
Hypothesis:
We believe that disruptions in RNA processing and the brain’s ability to adapt to them determine why some brain cells survive while others die in Parkinson’s disease.
Study Design:
We will study brain tissue from people with Parkinson’s, focusing on regions that are damaged and those that remain resilient, to map changes in RNA processing. Using advanced tools like RNA sequencing, spatial transcriptomics, and molecular imaging, we will identify which RNA changes matter most. We will then test these findings in stem cell–derived neurons that model PD in the lab, looking at how tRNA fragments, alpha-synuclein, and related proteins interact to trigger cell stress, inflammation, and toxicity.
Impact on Diagnosis/Treatment of Parkinson’s disease:
By identifying early RNA changes that drive PD, we may uncover new biomarkers for earlier diagnosis and new molecular targets for therapy.
Next Steps for Development:
If successful, these discoveries will guide the design of RNA-based drugs or interventions to restore healthy RNA balance and slow or stop PD progression.