Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons.

Abstract:

: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.

journal_name

Elife

journal_title

eLife

authors

Scheckel C,Imeri M,Schwarz P,Aguzzi A

doi

10.7554/eLife.62911

subject

Has Abstract

pub_date

2020-09-22 00:00:00

issn

2050-084X

pii

62911

journal_volume

9

pub_type

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