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.

中文翻译：

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朊病毒病期间的核糖体分析揭示了神经胶质而非神经元中的渐进性平移紊乱

朊病毒病是由 PrPSc 引起的，PrPSc 是一种自我复制的病理性错误折叠蛋白，主要在大脑中发挥毒性。PrPSc 的施用会导致强大的、可重复的和特定的疾病表现。在这里，我们应用了翻译核糖体亲和纯化和核糖体分析的组合，以细胞类型特异性和全基因组的方式识别疾病进展过程中与生物学相关的朊病毒诱导的变化。具有严重神经系统症状的晚期患病小鼠显示出星形胶质细胞和小胶质细胞的广泛改变。令人惊讶的是，我们仅检测到神经元平移谱的微小变化。朊病毒引起的胶质细胞改变与在其他神经退行性疾病中发现的改变重叠，表明类似的事件发生在广泛的病理中。