NCS1 overexpression restored mitochondrial activity and behavioral alterations in a zebrafish model of Wolfram syndrome.

ABSTRACT: Wolfram syndrome (WS) is a rare neurodegenerative disease resulting in deafness, optic atrophy, diabetes, and neurological disorders. Currently, no treatment is available for patients. The mutated gene, WFS1, encodes an endoplasmic reticulum (ER) protein, Wolframin. We previously reported that Wolframin regulated the ER-mitochondria Ca²⁺ transfer and mitochondrial activity by protecting NCS1 from degradation in patients' fibroblasts. We relied on a zebrafish model of WS, the wfs1ab ^KO line, to analyze the functional and behavioral impact of NCS1 overexpression as a novel therapeutic strategy. The wfs1ab ^KO line showed an increased locomotion in the visual motor and touch-escape responses. The absence of wfs1 did not impair

SUBMITTER: Crouzier L 

PROVIDER: S-EPMC9594121 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature