Identification of novel microglial signaling routes triggered by extracellular microRNAs and their impact on glioma

• Applicant: Professorin Dr. Seija Lehnardt
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 519177874

Microglia, the major immune cells in the brain, sense intrinsic and host-derived factors in both brain homeostasis and disease, which control their phenotype in a complex fashion. Here, we study a new group of such factors, namely microRNAs (miRNAs). It was recently discovered that these small non-coding, gene-regulating RNAs abundantly expressed in the brain, can act as ligands for the immune receptors Toll-like receptor 7 and 8 expressed in microglia. miRNAs are transferred from cell to cell and circulate in body fluids such as blood and cerebrospinal fluid. Based on this, we propose a novel mechanism of regulation of microglial function through sequence-specific binding of miRNAs to microglial receptors. The project’s aim is i) to identify the repertoire of miRNA-sensing receptors expressed in microglia, ii) to assess the potential of miRNAs to modify microglial function through binding to the respective receptor, and iii) to determine the contribution of the interaction between extracellular miRNA and microglial receptors to central nervous system (CNS) diseases such as glioblastoma (GBM), the most malignant brain tumor in adults. Deciphering the miRNAs’ mode of action as sequence-specific signaling molecules for microglia may open the way to the development of new diagnostic and therapeutic strategies in various CNS diseases, such as GBM.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Helmut Kettenmann