ArticlePLoS genetics2019
Ataxin2 functions via CrebA to mediate Huntingtin toxicity in circadian clock neurons.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Conserved role of Atx2 in JNK pathway activation.Cell death & disease · 2026Article
- Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies.Metabolic brain disease · 2026Review
- Article
- Reassessing the involvement of the CREB pathway in the circadian clock of Drosophila melanogaster.Npj biological timing and sleep · 2024Article
- Ataxin-2: a powerful RNA-binding protein.Discover oncology · 2024Review
- From wings to whiskers to stem cells: why every model matters in fragile X syndrome research.Journal of neurodevelopmental disorders · 2024Review
- Article
- Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease.Disease models & mechanisms · 2022Article
- The microtubule-associated protein Tau suppresses the axonal distribution of PDF neuropeptide and mitochondria in circadian clock neurons.Human molecular genetics · 2022Article
- Circadian rhythms in neurodegenerative disorders.Nature reviews. Neurology · 2022Review
- A C-terminal ataxin-2 disordered region promotes Huntingtin protein aggregation and neurodegeneration in Drosophila models of Huntington's disease.G3 (Bethesda, Md.) · 2021Article
- Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease.Nature communications · 2021Article
- Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease inMolecules and cells · 2020Article
- Article
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5 authors at 1 institution in 1 country.
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Abstract
Disrupted circadian rhythms is a prominent and early feature of neurodegenerative diseases including Huntington's disease (HD). In HD patients and animal models, striatal and hypothalamic neurons expressing molecular circadian clocks are targets of mutant Huntingtin (mHtt) pathogenicity. Yet how mHtt disrupts circadian rhythms remains unclear. In a genetic screen for modifiers of mHtt effects on circadian behavior in Drosophila, we discovered a role for the neurodegenerative disease gene Ataxin2 (Atx2). Genetic manipulations of Atx2 modify the impact of mHtt on circadian behavior as well as mHtt aggregation and demonstrate a role for Atx2 in promoting mHtt aggregation as well as mHtt-mediated neuronal dysfunction. RNAi knockdown of the Fragile X mental retardation gene, dfmr1, an Atx2 partner, also partially suppresses mHtt effects and Atx2 effects depend on dfmr1. Atx2 knockdown reduces the cAMP response binding protein A (CrebA) transcript at dawn. CrebA transcript level shows a prominent diurnal regulation in clock neurons. Loss of CrebA also partially suppresses mHtt effects on behavior and cell loss and restoration of CrebA can suppress Atx2 effects. Our results indicate a prominent role of Atx2 in mediating mHtt pathology, specifically via its regulation of CrebA, defining a novel molecular pathway in HD pathogenesis.
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