Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

ABSTRACT: Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. Comprehensive transcriptome analysis was employed to validate the capacity of three prioritized compounds to remodel th

ORGANISM(S): Homo sapiens

SUBMITTER: Jeff Kelly 

PROVIDER: E-GEOD-84636 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress