Significance of RNA Processing Bodies in Parkinson´s Disease

Parkinsons disease (PD) is the second most common neurodegenerative disorder after Alzheimers, affecting millions of people worldwide. While it is best known for its impact on movementsuch as tremors, stiffness, and slowed motionit also causes a range of non-motor symptoms, including sleep disturbances, memory problems, and mood changes. The disease is caused by the loss of dopamine- producing nerve cells and the accumulation of a protein called alpha-synuclein in the brain. So far, most research has focused on how alpha-synuclein damages the membranes of these brain cells. Our project offers a new perspective by exploring a different role of alpha-synuclein: how it affects the processing of genetic information inside brain cells. Specifically, we study messenger RNAs (mRNAs)the molecules that carry instructions from DNA to build proteins. Brain cells rely on precise control of mRNAs to stay healthy. We recently discovered that alpha-synuclein interacts with Processing Bodies (P-bodies), small structures inside cells that manage and degrade mRNAs. In Parkinsons disease, this interaction appears to malfunction, leading to the buildup of faulty or excessive mRNAs, which may stress or damage the cells. We aim to understand how P-bodies are involved in Parkinsons disease and whether problems in their function contribute to the death of nerve cells. To do this, we use stem-cell technology to grow human brain cells in the lab. This allows us to model Parkinsons disease and study how alpha- synuclein and P-bodies behave in both healthy and disease-like conditions. Our project has three main goals: 1. To study how P-bodies change in different types of brain cells affected by Parkinsons disease, 2. To understand how alpha-synuclein influences the breakdown of mRNAs, 3. To identify P-body-related genes that may either protect nerve cells or make them more vulnerable to damage. We use advanced tools, including custom-designed genetic switches and precise RNA-tracking techniques, to observe what happens inside cells in great detail. By comparing different types of brain cells, we hope to discover why some are more affected by Parkinsons disease than others. Ultimately, this research could open up new approaches to diagnosing or treating Parkinsons disease by targeting RNA regulationa process that has been overlooked until now. It may also provide insights into other brain disorders where similar mechanisms could be at play.