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.

The Relationship Between Irritable Bowel Syndrome and Metabolic Syndrome: A Systematic Review and Meta-Analysis of 49,662 Individuals.

Background: Studies have shown mixed results regarding the association between irritable bowel syndrome (IBS) and metabolic syndrome (MS); This study aimed to assess the susceptibility of IBS patients to MS and its individual components.

Methods: PubMed, Scopus, Embase, and Web of Science were searched on 1/1/2023. Eligible studies were screened, and data on study characteristics, IBS diagnostic criteria, and metabolic syndrome components were extracted.

Dysregulation of Retinal and Photoreceptor Structural Integrity Genes in ATF6 Retinal Organoids.

ATF6 is a key regulator of the unfolded protein response (UPR) pathway that maintains cellular homeostasis during ER stress. In people, loss of ATF6 function causes cone dysfunction, manifesting as achromatopsia (ACHM). Previously, we generated ACHM retinal organoids (ROs) from patient induced pluripotent stem cells (iPSCs) carrying mutant ATF6 variants and gene-edited ATF6-knockout (KO) human embryonic stem cells (hESCs).

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.