TY - JOUR T1 - Prions induce minor genome-wide translational changes in neurons compared to glia JF - bioRxiv DO - 10.1101/2020.06.26.172841 SP - 2020.06.26.172841 AU - Claudia Scheckel AU - Marigona Imeri AU - Petra Schwarz AU - Adriano Aguzzi Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/27/2020.06.26.172841.abstract N2 - Prion diseases are caused by PrPSc, a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrPSc causes a robust, reproducible and specific disease manifestation. Here we have applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease progression in a cell-type specific and genome-wide manner. Terminally diseased mice with severe neurological symptoms showed extensive alterations in astrocytes and microglia. Surprisingly, we detected only minor changes in the translational profiles of neurons. Prion-induced alterations in glia overlapped with those identified in other neurodegenerative diseases, suggesting that similar events occur in a broad spectrum of pathologies. Our results suggest that aberrant translation within glia may suffice to cause severe neurological symptoms and may even be the primary driver of prion disease.Competing Interest StatementThe authors have declared no competing interest. ER -