ArticleThe American journal of pathology2000
The cell cycle Cdc25A tyrosine phosphatase is activated in degenerating postmitotic neurons in Alzheimer's disease.
Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 98 citations in OpenAlex.
- Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs.Molecular neurobiology · 2024Review
- Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function.Science advances · 2023Article
- String/Cdc25 phosphatase is a suppressor of Tau-associated neurodegeneration.Disease models & mechanisms · 2023Article
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- 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
- Neuronal Cell Cycle Re-Entry Enhances Neuropathological Features in AppNLF Knock-In Mice.Journal of Alzheimer's disease : JAD · 2021Article
- Tau and DNA Damage in Neurodegeneration.Brain sciences · 2020Review
- Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development.Aging and disease · 2020Review
- "Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.Aging cell · 2020Review
- Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer.Journal of Alzheimer's disease : JAD · 2019Review
- Critical role of mitosis in spontaneous late-onset Alzheimer's disease; from a Shugoshin 1 cohesinopathy mouse model.Cell cycle (Georgetown, Tex.) · 2018Review
- Cdc25A phosphatase: a key cell cycle protein that regulates neuron death in disease and development.Cell death & disease · 2017Article
- Role and regulation of Cdc25A phosphatase in neuron death induced by NGF deprivation orCell death discovery · 2016Article
- Physiological and pathophysiological functions of cell cycle proteins in post-mitotic neurons: implications for Alzheimer's disease.Acta neuropathologica · 2015Review
- Neuronal cell cycle: the neuron itself and its circumstances.Cell cycle (Georgetown, Tex.) · 2015Review
- Telekin suppresses human hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via the p38 MAPK signaling pathway.Acta pharmacologica Sinica · 2014Article
- Cycle on Wheels: Is APP Key to the AppBp1 Pathway?Austin Alzheimer's and Parkinson's disease · 2014Article
- Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion.Oxidative medicine and cellular longevity · 2013Review
- Cell cycle activation and aneuploid neurons in Alzheimer's disease.Molecular neurobiology · 2012Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Cdc25 phosphatases play key roles in cell-cycle progression by activating cyclin-dependent kinases. The latter are absent from neurons that are terminally differentiated in adult brain. However, accumulation of mitotic phosphoepitopes, and re-expression and activation of the M phase regulator, Cdc2/cyclin B, have been described in neurons undergoing degeneration in Alzheimer's disease (AD). To explain this atypical mitotic activation in neurons we investigated the Cdc2-activating Cdc25A phosphatase in human brain. The structural hallmarks of AD neurodegeneration, neurofibrillary tangles and neuritic plaques, were prominently immunolabeled with Cdc25A antibodies. In addition numerous neurons without visible structural alterations were also intensely stained, whereas control brain was very weakly positive. After immunoprecipitation from control and AD tissue, we found that the tyrosine dephosphorylating activity of Cdc25A against exogenous Cdc2 substrate was elevated in AD. Accordingly, Cdc25A from AD tissue displayed increased immunoreactivity with the mitotic phosphoepitope-specific antibody, MPM-2, and co-localized with MPM-2 immunoreactivity in AD neurons. These data suggest that Cdc25A participates in mitotic activation during neurodegeneration. The involvement of Cdc25A in cellular transformation, modulation of the DNA damage checkpoint, and linkage of mitogenic signaling to cell cycle machinery, also implicates one of these cell-cycle pathways in AD pathogenesis.
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