ArticleProceedings of the National Academy of Sciences of the United States of America2014
Topoisomerase 1 inhibition reversibly impairs synaptic function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- Article
- The psychedelic psilocybin and light exposure have similar and synergistic effects on gene expression patterns in the visual cortex.Molecular brain · 2025Article
- How do neurons live long and healthy? The mechanism of neuronal genome integrity.Frontiers in neuroscience · 2025Review
- The Intellectual Disability Risk GeneThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Parallel gene size and isoform expansion of ancient neuronal genes.Current biology : CB · 2024Article
- MeCP2 represses the activity of topoisomerase IIβ in long neuronal genes.Cell reports · 2023Article
- Opioid induces increased DNA damage in prefrontal cortex and nucleus accumbens.Pharmacology, biochemistry, and behavior · 2023Article
- The Interactions of the 70 kDa Fragment of Cell Adhesion Molecule L1 with Topoisomerase 1, Peroxisome Proliferator-Activated Receptor γ and NADH Dehydrogenase (Ubiquinone) Flavoprotein 2 Are Involved in Gene Expression and Neuronal L1-Dependent Functions.International journal of molecular sciences · 2023Article
- MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs.Cell stem cell · 2021Article
- The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders.Cancers · 2020Review
- Deletion of Topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration.Nature communications · 2020Article
- Prenatal treatment path for angelman syndrome and other neurodevelopmental disorders.Autism research : official journal of the International Society for Autism Research · 2020Review
- IPSC Models of Chromosome 15Q Imprinting Disorders: From Disease Modeling to Therapeutic Strategies.Advances in neurobiology · 2020Article
- Transcriptional supercoiling boosts topoisomerase II-mediated knotting of intracellular DNA.Nucleic acids research · 2019Article
- The Route to 'Chemobrain' - Computational probing of neuronal LTP pathway.Scientific reports · 2019Article
- Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function.Autism research : official journal of the International Society for Autism Research · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Topotecan is a topoisomerase 1 (TOP1) inhibitor that is used to treat various forms of cancer. We recently found that topotecan reduces the expression of multiple long genes, including many neuronal genes linked to synapses and autism. However, whether topotecan alters synaptic protein levels and synapse function is currently unknown. Here we report that in primary cortical neurons, topotecan depleted synaptic proteins that are encoded by extremely long genes, including Neurexin-1, Neuroligin-1, Cntnap2, and GABA(A)β3. Topotecan also suppressed spontaneous network activity without affecting resting membrane potential, action potential threshold, or neuron health. Topotecan strongly suppressed inhibitory neurotransmission via pre- and postsynaptic mechanisms and reduced excitatory neurotransmission. The effects on synaptic protein levels and inhibitory neurotransmission were fully reversible upon drug washout. Collectively, our findings suggest that TOP1 controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission.
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Registered trials
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.