ArticleCell death and differentiation2015
Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- Glycogen Synthase Kinase-3β, NLRP3 Inflammasome, and Alzheimer's Disease.Current medical science · 2023Review
- Notch mediates the glycolytic switch via PI3K/Akt signaling to support embryonic development.Cellular & molecular biology letters · 2023Article
- Cerebellar granule neurons induce Cyclin D1 before the onset of motor symptoms in Huntington's disease mice.Acta neuropathologica communications · 2023Article
- Butanol Extract of Tinospora cordifolia Alleviates Acute Sleep Deprivation-Induced Impairments in Cognitive Functions and Neuromuscular Coordination in Middle-Aged Female Rats.Neuromolecular medicine · 2022Article
- Dual-Specificity Phosphatase 15 (DUSP15) Modulates Notch Signaling by Enhancing the Stability of Notch Protein.Molecular neurobiology · 2021Article
- Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration.Frontiers in cell and developmental biology · 2021Review
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- Genetic Dissection of Alzheimer's Disease UsingInternational journal of molecular sciences · 2020Review
- The roles and mechanisms of YTH domain-containing proteins in cancer development and progression.American journal of cancer research · 2020Review
- N-methyl-D-aspartate receptor-mediated calcium influx connects amyloid-β oligomers to ectopic neuronal cell cycle reentry in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Article
- U1 snRNP Alteration and Neuronal Cell Cycle Reentry in Alzheimer Disease.Frontiers in aging neuroscience · 2018Review
- Involvement of AMPK in regulating the degradation of MAD2B under high glucose in neuronal cells.Journal of cellular and molecular medicine · 2017Article
- Involvement of Fra-1 in Retinal Ganglion Cell Apoptosis in Rat Light-Induced Retina Damage Model.Cellular and molecular neurobiology · 2017Article
- Jagged1 Is Altered in Alzheimer's Disease and Regulates Spatial Memory Processing.Frontiers in cellular neuroscience · 2017Article
- Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration.Nature neuroscience · 2016Article
- Notch1 hallmarks fibrillary depositions in sporadic Alzheimer's disease.Acta neuropathologica communications · 2016Article
- Alzheimer's Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms.Frontiers in neuroscience · 2016Review
- Cdk5-mediated inhibition of APC/C-Cdh1 switches on the cyclin D1-Cdk4-pRb pathway causing aberrant S-phase entry of postmitotic neurons.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurological disorders such as Alzheimer's disease, stroke and epilepsy are currently marred by the lack of effective treatments to prevent neuronal death. Erroneous cell cycle reentry (CCR) is hypothesized to have a causative role in neurodegeneration. We show that forcing S-phase reentry in cultured hippocampal neurons is sufficient to induce neurodegeneration. We found that kainic-acid treatment in vivo induces erroneous CCR and neuronal death through a Notch-dependent mechanism. Ablating Notch signaling in neurons provides neuroprotection against kainic acid-induced neuronal death. We further show that kainic-acid treatment activates Notch signaling, which increases the bioavailability of CyclinD1 through Akt/GSK3β pathway, leading to aberrant CCR via activation of CyclinD1-Rb-E2F1 axis. In addition, pharmacological blockade of this pathway at critical steps is sufficient to confer resistance to kainic acid-induced neurotoxicity in mice. Taken together, our results demonstrate that excitotoxicity leads to neuronal death in a Notch-dependent manner through erroneous CCR.
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Registered trials
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