ArticleMolecular biology of the cell2011
Nuclear envelope dispersion triggered by deregulated Cdk5 precedes neuronal death.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Tau oligomerization induces nuclear lamina invagination and chromatin remodeling in Alzheimer's disease.Acta neuropathologica · 2026Article
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- Dynamic Post-translational Modifications of Nuclear Lamins in Cellular Function and Pathophysiology.Sub-cellular biochemistry · 2025Review
- Genetically Encoded Fluorescence Resonance Energy Transfer Biosensor for Live-Cell Visualization of Lamin A Phosphorylation at Serine 22.Biomaterials research · 2024Article
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- Regulatory role of cathepsin L in induction of nuclear laminopathy in Alzheimer's disease.Aging cell · 2022Article
- Post-Translational Modification of Lamins: Mechanisms and Functions.Frontiers in cell and developmental biology · 2022Review
- Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models.Journal of biomedical science · 2021Article
- Components and Mechanisms of Nuclear Mechanotransduction.Annual review of cell and developmental biology · 2021Review
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- When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease.International journal of molecular sciences · 2021Review
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- Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration.International journal of molecular sciences · 2021Review
- Phosphorylation-dependent regulation of SPOP by LIMK2 promotes castration-resistant prostate cancer.British journal of cancer · 2021Article
- Differential involvement of caspase-6 in amyloid-β-induced fragmentation of lamin A and B.Biochemistry and biophysics reports · 2020Article
- Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies.Nucleus (Austin, Tex.) · 2020Review
- Molecular Interplay between AURKA and SPOP Dictates CRPC Pathogenesis via Androgen Receptor.Cancers · 2020Article
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- Gene expression modulation by the linker of nucleoskeleton and cytoskeleton complex contributes to proteostasis.Aging cell · 2019Article
- The Role of Phosphatases in Nuclear Envelope Disassembly and Reassembly and Their Relevance to Pathologies.Cells · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear fragmentation is a common feature in many neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we show that nuclear lamina dispersion is an early and irreversible trigger for cell death initiated by deregulated Cdk5, rather than a consequence of apoptosis. Cyclin-dependent kinase 5 (Cdk5) activity is significantly increased in AD and contributes to all three hallmarks: neurotoxic amyloid-β (Aβ), neurofibrillary tangles (NFT), and extensive cell death. Using Aβ and glutamate as the neurotoxic stimuli, we show that deregulated Cdk5 induces nuclear lamina dispersion by direct phosphorylation of lamin A and lamin B1 in neuronal cells and primary cortical neurons. Phosphorylation-resistant mutants of lamins confer resistance to nuclear dispersion and cell death on neurotoxic stimulation, highlighting this as a major mechanism for neuronal death. Rapid alteration of lamin localization pattern and nuclear membrane change are further supported by in vivo data using an AD mouse model. After p25 induction, the pattern of lamin localization was significantly altered, preceding neuronal death, suggesting that it is an early pathological event in p25-inducible transgenic mice. Importantly, lamin dispersion is coupled with Cdk5 nuclear localization, which is highly neurotoxic. Inhibition of nuclear dispersion rescues neuronal cells from cell death, underscoring the significance of this event to Cdk5-mediated neurotoxicity.
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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.