ArticlePLoS genetics2018
Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Characterization of Novel WFS1 Variants in Three Diabetes Pedigrees.Journal of diabetes · 2025Article
- Supplementation of essential amino acids suppresses age-associated sleep loss and sleep fragmentation but not loss of rhythm strength under yeast-restricted malnutrition in Drosophila.Journal of biochemistry · 2025Article
- Expanding the spectrum of white matter abnormalities in Wolfram syndrome: a retrospective review.Frontiers in neurology · 2025Article
- The WFS1-ZnT3-ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Beyond Wolfram Syndrome 1: TheBiomolecules · 2024Review
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Review
- Wolfram syndrome 1 regulates sleep in dopamine receptor neurons by modulating calcium homeostasis.PLoS genetics · 2023Article
- Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.Molecular psychiatry · 2023Article
- Article
- Markers and mechanisms of death inFrontiers in aging · 2023Article
- Case Report: A novel mutation inFrontiers in genetics · 2023Article
- Wolfram syndrome 1b mutation suppresses Mauthner-cell axon regeneration via ER stress signal pathway.Acta neuropathologica communications · 2022Article
- NCS1 overexpression restored mitochondrial activity and behavioral alterations in a zebrafish model of Wolfram syndrome.Molecular therapy. Methods & clinical development · 2022Article
- Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in aging mice.Cell reports · 2022Article
- A conserved long-distance telomeric silencing mechanism suppresses mTOR signaling in aging human fibroblasts.Science advances · 2022Article
- Dysregulated CaCells · 2022Review
- Wolframin is a novel regulator of tau pathology and neurodegeneration.Acta neuropathologica · 2022Article
- Effect of Riluzole on the Expression of HCN2 in Dorsal Root Ganglion Neurons of Diabetic Neuropathic Pain Rats.Journal of healthcare engineering · 2022Article
- Human iPSC-derived neurons reveal early developmental alteration of neurite outgrowth in the late-occurring neurodegenerative Wolfram syndrome.American journal of human genetics · 2021Article
- A mutant wfs1 zebrafish model of Wolfram syndrome manifesting visual dysfunction and developmental delay.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.
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