Study Rationale: Inflammation is a common event in neurodegenerative diseases such as Parkinson's disease (PD), although its source remains unclear. Many different factors can potentially trigger inflammation in the nervous system. One possible candidate is the activation of transposable elements, which are virus-like gene fragments that are abundant in our DNA and are remnants of ancestral viral infections. Whereas these transposable elements are normally inactive, certain stressors can reactivate them, leading to a potential immune response that promotes a chronic inflammatory state.
Hypothesis: We hypothesize that transposable elements are active in the brain cells of people with PD and that this activity can induce inflammation in the nervous system and contribute to PD pathology.
Study Design: We will first search for evidence of transposable element activity in PD brain tissue using the latest molecular biology approaches. These experiments will also allow us to determine whether cells that show increased transposable element activity also show increased signs of inflammation. Because cells of the central nervous system (neurons, astrocytes and microglia) can be grown in culture in the laboratory, we can use cultured cells to explore the mechanism behind this phenomenon. We will test whether manipulations that activate transposable elements in these cells also trigger an immune response and vice versa.
Impact on Diagnosis/Treatment of Parkinson’s disease: If we find that transposable element activity contributes to the inflammation associated with PD, this could lead to the development of novel anti-inflammatory drugs that block inflammation by blocking this activation.
Next Steps for Development: Our study focuses on understanding one of the basic triggers that may cause inflammation in PD and the molecular mechanisms behind it. Our results may have direct implications for clinical applications in the medium term.