ArticleScientific reports2018
Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
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- Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer's disease by meta-analysis and adaptive boosting ensemble learning.Alzheimer's research & therapy · 2021Pooled it
- Mechanical compression induces neuronal apoptosis, reduces synaptic activity, and promotes glial neuroinflammation in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Single-cell Spatial Transcriptional Profiling Uncovers Heterogeneous Cellular Responses to Pathogenic Tau in a Mouse Model of Neurodegeneration.bioRxiv : the preprint server for biology · 2025Article
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- From Fundamentals to Innovation in Alzheimer's Disease: Molecular Findings and Revolutionary Therapies.International journal of molecular sciences · 2024Review
- Development of an accelerated cellular model for early changes in Alzheimer's disease.Scientific reports · 2023Article
- Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?Reports (MDPI) · 2023Review
- Neural cell state shifts and fate loss in ageing and age-related diseases.Nature reviews. Neurology · 2023Review
- DNA Damage Response-Associated Cell Cycle Re-Entry and Neuronal Senescence in Brain Aging and Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Molecular Connections between DNA Replication and Cell Death in β-Amyloid-Treated Neurons.Current neuropharmacology · 2023Article
- Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model.Current research in neurobiology · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Role of Neddylation in Neurodegenerative Diseases.NeuroSci · 2022Review
- Pathological Nuclear Hallmarks in Dentate Granule Cells of Alzheimer's Patients: A Biphasic Regulation of Neurogenesis.International journal of molecular sciences · 2022Article
- E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging.International journal of molecular sciences · 2022Review
- A Mutant Variant of E2F4 Triggers Multifactorial Therapeutic Effects in 5xFAD Mice.Molecular neurobiology · 2022Article
- Identifying Biomarkers of Alzheimer's Disease via a Novel Structured Sparse Canonical Correlation Analysis Approach.Journal of molecular neuroscience : MN · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Cell cycle reentry followed by neuronal hyperploidy and synaptic failure are two early hallmarks of Alzheimer's disease (AD), however their functional connection remains unexplored. To address this question, we induced cell cycle reentry in cultured cortical neurons by expressing SV40 large T antigen. Cell cycle reentry was followed by hyperploidy in ~70% of cortical neurons, and led to progressive axon initial segment loss and reduced density of dendritic PSD-95 puncta, which correlated with diminished spike generation and reduced spontaneous synaptic activity. This manipulation also resulted in delayed cell death, as previously observed in AD-affected hyperploid neurons. Membrane depolarization by high extracellular potassium maintained PSD-95 puncta density and partially rescued both spontaneous synaptic activity and cell death, while spike generation remained blocked. This suggests that AD-associated hyperploid neurons can be sustained in vivo if integrated in active neuronal circuits whilst promoting synaptic dysfunction. Thus, cell cycle reentry might contribute to cognitive impairment in early stages of AD and neuronal death susceptibility at late stages.
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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.