ArticleCell cycle (Georgetown, Tex.)2011
Alzheimer Aβ disrupts the mitotic spindle and directly inhibits mitotic microtubule motors.
Article in Cell cycle (Georgetown, Tex.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- The deficiency of KIF2C leads to abnormal distribution of cortical neurons and behavioral deficits in mice.iScience · 2026Article
- Blood measure of neuronal death is exponentially higher with age, especially in females, and halted in Alzheimer's disease by GM-CSF treatment.Cell reports. Medicine · 2026Article
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- Research progress of kinesin family in neurological diseases.Frontiers in cellular neuroscience · 2025Review
- Eg5 and Diseases: From the Well-Known Role in Cancer to the Less-Known Activity in Noncancerous Pathological Conditions.Biochemistry research international · 2024Review
- Cellular response to β-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics.Animal models and experimental medicine · 2023Review
- IncreasediScience · 2022Article
- KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization.eLife · 2022Article
- The Gαq/phospholipase Cβ signaling system represses tau aggregation.Cellular signalling · 2020Article
- "Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.Aging cell · 2020Review
- Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders.Frontiers in genetics · 2019Article
- Alzheimer's Disease and Its Potential Alternative Therapeutics.Journal of Alzheimer's disease & Parkinsonism · 2019Article
- Mitotic defects lead to neuronal aneuploidy and apoptosis in frontotemporal lobar degeneration caused by MAPT mutations.Molecular biology of the cell · 2018Article
- An integrated bioinformatical analysis to evaluate the role of KIF4A as a prognostic biomarker for breast cancer.OncoTargets and therapy · 2018Article
- Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.Molecular pharmacology · 2016Article
- Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death.Disease models & mechanisms · 2016Article
- Aβ 1-40 enhances the proliferation of human diploid fibroblasts.Neurobiology of aging · 2016Article
- Role of Trisomy 21 Mosaicism in Sporadic and Familial Alzheimer's Disease.Current Alzheimer research · 2016Review
- Beyond Trisomy 21: Phenotypic Variability in People with Down Syndrome Explained by Further Chromosome Mis-segregation and Mosaic Aneuploidy.Journal of Down Syndrome & chromosome abnormalities · 2016Article
- Intracellular amyloid β oligomers impair organelle transport and induce dendritic spine loss in primary neurons.Acta neuropathologica communications · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Chromosome mis-segregation and aneuploidy are greatly induced in Alzheimer's disease and models thereof by mutant forms of the APP and PS proteins and by their product, the Ab peptide. Here we employ human somatic cells and Xenopus egg extracts to show that Aβ impairs the assembly and maintenance of the mitotic spindle. Mechanistically, these defects result from Aβ's inhibition of mitotic motor kinesins, including Eg5, KIF4A and MCAK. In vitro studies show that oligomeric Aβ directly inhibits recombinant MCAK by a noncompetitive mechanism. In contrast, inhibition of Eg5 and KIF4A is competitive with respect to both ATP and microtubules, indicating that Aβ interferes with their interactions with the microtubules of the mitotic spindle. Consistently, increased levels of polymerized microtubules or of the microtubule stabilizing protein Tau significantly decrease the inhibitory effect of Aβ on Eg5 and KIF4A. Together, these results indicate that by disrupting the interaction between specific kinesins and microtubules and by exerting a direct inhibitory effect on the motor activity, excess Ab deregulates the mechanical forces that govern the spindle and thereby leads to the generation of defective mitotic structures. The resulting defect in neurogenesis can account for the over 30% aneuploid/hyperploid, degeneration-prone neurons observed in Alzheimer disease brain. The finding of mitotic motors including Eg5 in mature post-mitotic neurons implies that their inhibition by Ab may also disrupt neuronal function and plasticity.
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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.