Janus Kinase 1 Is Required for Transcriptional Reprograming of Murine Astrocytes in Response to Endoplasmic Reticulum Stress.

ABSTRACT: Neurodegenerative diseases are associated with the accumulation of misfolded proteins in the endoplasmic reticulum (ER), leading to ER stress. To adapt, cells initiate the unfolded protein response (UPR). However, severe or unresolved UPR activation leads to cell death and inflammation. The UPR is initiated, in part, by the trans-ER membrane kinase PKR-like ER kinase (PERK). Recent evidence indicates ER stress and inflammation are linked, and we have shown that this involves PERK-dependent signaling via Janus Kinase (JAK) 1. This signaling provokes the production of soluble inflammatory mediators such as interleukin-6 (IL-6) and chemokine C-C motif ligand 2 (CCL2). We, therefore, hypothesized that JAK1 may control widespread transcriptional changes in response to ER stress. Here, us

SUBMITTER: Sims SG 

PROVIDER: S-EPMC6797841 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature