Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models.

ABSTRACT: The Wolfram syndrome is a rare autosomal recessive disease affecting many organs with life-threatening consequences; currently, no treatment is available. The disease is caused by mutations in the WSF1 gene, coding for the protein wolframin, an endoplasmic reticulum (ER) transmembrane protein involved in contacts between ER and mitochondria termed as mitochondria-associated ER membranes (MAMs). Inherited mutations usually reduce the protein's stability, altering its homeostasis and ultimately reducing ER to mitochondria calcium ion transfer, leading to mitochondrial dysfunction and cell death. In this study, we found that activation of the sigma-1 receptor (S1R), an ER-resident protein involved in calcium ion transfer, could counteract the functional alterations of MAMs due to wolfr

SUBMITTER: Crouzier L 

PROVIDER: S-EPMC9516885 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature