ArticleHuman molecular genetics2017
Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of fragile X-associated tremor/ataxia syndrome.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025).Frontiers in bioengineering and biotechnology · 2026Review
- Progression of fragile X-associated tremor/ataxia syndrome revealed by subtype and stage inference.Brain communications · 2026Article
- Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function.Nature communications · 2025Article
- Review
- Article
- Article
- Clinical implications of somatic allele expansion in female FMR1 premutation carriers.Scientific reports · 2023Article
- Smooth Muscle Cells of Dystrophic (mdx) Mice Are More Susceptible to Hypoxia; The Protective Effect of Reducing CaBiomedicines · 2023Article
- Profiling human pathogenic repeat expansion regions by synergistic and multi-level impacts on molecular connections.Human genetics · 2023Article
- Insights into the role of intracellular calcium signaling in the neurobiology of neurodevelopmental disorders.Frontiers in neuroscience · 2023Review
- Gene×environment interactions in autism spectrum disorders.Current topics in developmental biology · 2023Review
- Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers.Genes · 2022Article
- Autism spectrum disorder in the fragile X premutation state: possible mechanisms and implications.Journal of neurology · 2022Review
- ATM rules neurodevelopment and glutamatergic transmission in the hippocampus but not in the cortex.Cell death & disease · 2022Article
- Mechanisms of theInternational journal of molecular sciences · 2022Review
- Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions.Nature reviews. Neurology · 2022Review
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome.Frontiers in genetics · 2022Review
- Chronic Elevation of Skeletal Muscle [CaFrontiers in physiology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels. Resting cytoplasmic calcium concentration ([Ca2+]i) in cultured preCGG hippocampal neurons is chronically elevated, 3-fold compared to Wt; elevated ROS and abnormal glutamatergic responses are detected at 14 DIV. Elevated µ-calpain activity and a higher p25/p35 ratio in the cortex of preCGG young adult mice indicate abnormal Cdk5 regulation. In support, the Cdk5 substrate, ATM, is upregulated by 1.5- to 2-fold at P0 and 6 months in preCGG brain, as is p-Ser1981-ATM. Bax:Bcl-2 is 30% higher in preCGG brain, indicating a greater vulnerability to apoptotic activation. Elevated [Ca2+]i, ROS, and DDR signals are normalized with dantrolene. Chronic [Ca2+]i dysregulation amplifies Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to neurodegeneration in preCGG brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.