Developmental hypomyelination in Wolfram syndrome: new insights from neuroimaging and gene expression analyses.

ABSTRACT: Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primari

SUBMITTER: Samara A 

PROVIDER: S-EPMC6889680 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature