How the Plk2 enzyme controls alpha‑synuclein at connections between brain cells
Polo-like-kinase-2-dependent α-Synuclein Serine-129 Phosphorylation: a Physiological RoleDuring Synaptic Activity
Researchers are looking at how an enzyme called Plk2 adds a chemical tag to alpha‑synuclein at nerve cell connections to better understand Parkinson’s, Lewy body dementia, and related Alzheimer cases.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Brigham and Women's Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11345147 on NIH RePORTER |
What this research studies
This project looks at a specific chemical change (phosphorylation at serine‑129) on the brain protein alpha‑synuclein that is often seen in Parkinson’s and Lewy body dementia. Scientists will use neuron and brain tissue experiments, plus animal and cell models, to see whether the enzyme Plk2 adds this chemical tag in response to nerve activity and how that affects alpha‑synuclein’s normal role at synapses. They will turn Plk2 activity up or down and measure synaptic function, alpha‑synuclein behavior, and markers of aggregation to determine whether the phosphorylation helps or harms neurons. The team aims to identify molecular signs that could guide future drugs or tests for synuclein‑related diseases.
Who could benefit from this research
Good fit: People diagnosed with Parkinson’s disease, dementia with Lewy bodies, multiple‑system atrophy, or Alzheimer’s patients suspected of having alpha‑synuclein pathology would be the most relevant candidates for future participation or sample donation.
Not a fit: Patients whose conditions do not involve alpha‑synuclein pathology (for example pure vascular dementia or non‑synuclein forms of cognitive impairment) are unlikely to benefit directly from this specific research.
Why it matters
Potential benefit: If successful, the work could point to new drug targets or biomarkers to prevent, slow, or detect alpha‑synuclein pathology in Parkinson’s disease, Lewy body dementia, and some Alzheimer’s cases.
How similar studies have performed: Other studies have found that serine‑129 phosphorylation is abundant in disease lesions and can change with neural activity, but whether it is protective or harmful remains unclear, so this work builds on existing observations while addressing an unresolved question.
Where this research is happening
Boston, United States
- Brigham and Women's Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Dettmer, Ulf — Brigham and Women's Hospital
- Study coordinator: Dettmer, Ulf
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.