On March 25, Fumihiko Urano, MD, PhD and colleagues had their research titled “Loss of Function of WFS1 Causes ER Stress-Mediated Inflammation in Pancreatic Beta-Cells,” published in “Frontiers in Endocrinology.”
Wolfram syndrome is “a rare genetic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and progressive neurodegeneration.” The main cause of Wolfram syndrome is when pathogenic variants appear in the WFS1 gene, causing it loss of function. This leads to regulatory issues in the production and secretion of insulin. Not only that, but ER calcium begins to deplete and cytosolic calpains activate — resulting in the activation of apoptosis cascades.
Urano’s research shows that WFS1-deficiency enhances gene expression which leads to ER-stress and cell death. It also demonstrates that WFS1 regulates anti-inflammatory responses.
In conclusion, “inflammation plays an essential role in the progression of β-cell death and diabetes in Wolfram syndrome. The pathways involved in ER stress-mediated inflammation provide potential therapeutic targets for the treatment of Wolfram syndrome.”