ArticleMolecular neurodegeneration2015
Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 40 citations in OpenAlex.
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- TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.The FEBS journal · 2026Review
- Tissue distribution of cysteine string protein/DNAJC5 in C. elegans analysed by CRISPR/Cas9-mediated tagging of endogenous DNJ-14.Cell and tissue research · 2024Article
- A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.Human molecular genetics · 2023Article
- Identifying longevity associated genes by integrating gene expression and curated annotations.PLoS computational biology · 2020Article
- Network Simulations Reveal Molecular Signatures of Vulnerability to Age-Dependent Stress and Tau Accumulation.Frontiers in molecular biosciences · 2020Article
- Article
- A Caenorhabditis elegans assay of seizure-like activity optimised for identifying antiepileptic drugs and their mechanisms of action.Journal of neuroscience methods · 2018Article
- α-Methyl-α-phenylsuccinimide ameliorates neurodegeneration in a C. elegans model of TDP-43 proteinopathy.Neurobiology of disease · 2018Article
- Current Perspective in the Discovery of Anti-aging Agents from Natural Products.Natural products and bioprospecting · 2017Review
- Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans.Scientific reports · 2017Article
- The stress response factor daf-16/FOXO is required for multiple compound families to prolong the function of neurons with Huntington's disease.Scientific reports · 2017Article
- Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression.Molecular neurodegeneration · 2015Article
- Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases.Chemistry Central journal · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMany neurodegenerative diseases are associated with protein misfolding/aggregation. Treatments mitigating the effects of such common pathological processes, rather than disease-specific symptoms, therefore have general therapeutic potential.
resultsHere we report that the anti-epileptic drug ethosuximide rescues the short lifespan and chemosensory defects exhibited by C. elegans null mutants of dnj-14, the worm orthologue of the DNAJC5 gene mutated in autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. It also ameliorates the locomotion impairment and short lifespan of worms expressing a human Tau mutant that causes frontotemporal dementia. Transcriptomic analysis revealed a highly significant up-regulation of DAF-16/FOXO target genes in response to ethosuximide; and indeed RNAi knockdown of daf-16 abolished the therapeutic effect of ethosuximide in the worm dnj-14 model. Importantly, ethosuximide also increased the expression of classical FOXO target genes and reduced protein aggregation in mammalian neuronal cells.
conclusionsWe have revealed a conserved neuroprotective mechanism of action of ethosuximide from worms to mammalian neurons. Future experiments in mouse neurodegeneration models will be important to confirm the repurposing potential of this well-established anti-epileptic drug for treatment of human neurodegenerative diseases.
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