Transcriptomic Profiling of Small Molecule Atf6 Modulators in the Retina.

The Unfolded Protein Response (UPR) maintains endoplasmic reticulum (ER) homeostasis and is essential for retinal health. Activating Transcription Factor 6 (ATF6) controls a key UPR branch and upregulates genes that mitigate ER stress. Small molecule modulators of ATF6 have been characterized in cell culture models that increase or decrease the amount of the cleaved, transcriptional activator domain of ATF6 generated from the full-length precursor.

Vulnerability of the Nrl Cone-Dominant Retina to Endoplasmic Reticulum Stress.

Neural retina leucine zipper (NRL) is essential for the development of rods. The Nrl knockout (Nrl) mouse develops a cone-rich retina which facilitates investigations of cone biology. Previously, we identified the endoplasmic reticulum (ER) stress response gene ATF6 as a cause of cone dysfunction in people.

Ethnic variation and structure-function analysis of tauopathy-associated alleles.

EIF2AK3, also known as PERK, plays a pivotal role in cellular proteostasis, orchestrating the Unfolded Protein Response (UPR) and Integrated Stress Response (ISR) pathways. In addition to its central position in intracellular stress regulation, human GWAS identify EIF2AK3 as a risk factor in tauopathies, neurodegenerative diseases caused by aberrant tau protein accumulation. Guided by these genomic indicators, our investigation systematically analyzed human PERK variants, focusing on those with potential tauopathy linkages.