Investigating microglial involvement in α-synuclein dynamics in Parkinson’s disease pathology using a human iPSC derived neural tri-lineage model

• Applicant: Alexandra de la Porte
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559239269

Our understanding of how microglia respond to α-synuclein aggregates and their involvement in neuronal degeneration remains limited. While microglia are known to play an active role in neuroinflammation and the transmission of α-synuclein between cells, the precise mechanisms involved are still unclear. This project aims to explore these interactions by studying the impact of microglia on α-synuclein dynamics in vitro, using an α-synuclein-fibril model in combination with a human induced pluripotent stem cell-derived neural tri-culture system. The tri-culture model, composed of neurons, astrocytes, and microglia, closely replicates the brain’s cellular environment, allowing for a detailed investigation of how microglia influence α-syn uptake, aggregation, propagation, and clearance, which are key processes implicated in Parkinson's disease pathology. By leveraging these advanced stem cell models and molecular techniques, this study seeks to provide deeper insights into microglial roles in disease progression and pave the way for developing future therapeutic strategies targeting microglial functions.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Marius Wernig, Ph.D.