A role for astroglia in prion diseases

Abstract

In this issue of JEM, Krejciova et al. (https://doi.org/10.1084/jem.20161547) report that astrocytes derived from human iPSCs can replicate human CJD prions. These observations provide a new, potentially very valuable model for studying human prions in cellula and for identifying antiprion compounds that might serve as clinical candidates. Furthermore, they add to the evidence that astrocytes may not be just innocent bystanders in prion diseases.

Insight from Adriano Aguzzi and Yingjun Liu

(a) Human iPSC-derived astrocyte supports the replication of CJD prions. In contrast to differentiated astrocytes, however, human iPSC-derived APCs failed to replicate human prions despite expression of PrP^C. It is still unclear whether human iPSC-derived neurons, oligodendrocytes, and their precursors (NPC and OPC, respectively) are capable of supporting human prion replication. (b) Rodent studies have showed that differentiated neurons and astrocytes, but neither undifferentiated neurospheres nor oligodendrocytes, support prion replication.