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Comments on Kyriakakis, Emmanouil et al. (2017) International Worm Meeting "A C. elegans model of Wolfram Syndrome type 2." (0)
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Kyriakakis, Emmanouil, Ploumi, Christina, & Tavernarakis, Nektarios (2017). A C. elegans model of Wolfram Syndrome type 2 presented in International Worm Meeting. Unpublished information; cite only with author permission.
Wolfram syndrome (WS) is a rare autosomal neurodegenerative disorder, characterized by early juvenile diabetes mellitus, a gradual loss of vision due optic nerve atrophy, deafness and often behavioral and mental changes. The average life expectancy is 30 years due to systemic complications. Treatment is merely symptomatic and supportive. There are two genetics forms of WS; type 1 is caused by mutations in the WFS1 (wolframin) gene, whereas WS type 2 is caused by mutations in the CISD2 gene. The C. elegans cisd-1 gene encodes a homolog of the mammalian CISD2, based on sequence analysis and the presence of the conserved iron sulfur domain. Lesion of cisd-1 recapitulates key features of CISD2 loss associated with WS type 2, including lifespan shortening and neurodegeneration. Intriguingly, dietary restriction (DR) completely reverses the detrimental effects of CISD-1 deficiency on longevity. This effect is at least in part due to autophagy induction. In addition, cellular proteostasis mechanisms are deferentially affected by CISD-1. The mitochondrial unfolded protein response (UPRmito) is significantly suppressed, while the endoplasmic reticulum UPRER is upregulated during ER stress. The heat shock response remains unaffected. These findings suggest an involvement of CISD-1 in organelle-specific proteome homeostasis. The C. elegans WS model will facilitate elucidation of the molecular mechanisms underlying WS pathogenesis and provide a platform for drug discovery.
Affiliations:
- Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas
- Department of Basic Sciences, Faculty of Medicine, University of Crete, Greece
- Biozentrum, University of Basel, Basel, Switzerland