Activation of Transposable Elements as a Trigger of Neuroinflammation in Parkinson’s Disease

Study Rationale:
Inflammation is a common event in Parkinson’s disease (PD), but its source remains unclear. There are many candidates that could cause inflammation in the nervous system. One likely candidate involves the activity of transposable elements, which are viral-like gene fragments left over from viral infections. While transposable elements are normally inactive, certain stressors can reactivate these genes, leading to a potential immune response, including inflammation.

Hypothesis:
This study will seek to determine whether transposable elements are active in tissues from patients with Parkinson’s disease and whether this activity can induce inflammation in the nervous system.

Study Design:
We will first look for evidence of transposable element activity using single-cell RNA sequencing of tissues from people with Parkinson’s disease. This particular experiment will also allow us to determine whether patient cells that show more transposable element activity also show increased signs of inflammation. Because cells of the central nervous system (neurons, astrocytes and microglia) can be grown in a laboratory culture system, we can also test whether manipulations that induce transposable element activity in these cells also causes an immune response that would result in inflammation. This would suggest that blocking transposon activity could block inflammation.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
If we can determine that transposable element activity is the trigger for inflammation in the setting of Parkinson’s disease, it would open several unexplored options for treatment. This would enable the targeted development of anti-inflammatory or anti-viral compounds effective against the specific triggers seen in PD patient samples.

Next Steps for Development:
While this study is focused on understanding the basic triggers that cause inflammation in PD, the results could still have impact on clinical applications. This would include the development of biomarkers of transposable elements activity that could be detected at the time of diagnosis, as well as the development of compounds effective in blocking their activity.