ArticleInternational journal of clinical and experimental pathology2008
Retinoblastoma protein phosphorylation at multiple sites is associated with neurofibrillary pathology in Alzheimer disease.
Article in International journal of clinical and experimental pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 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
- 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
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- Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation.Current research in neurobiology · 2022Review
- Neuronal Cell Cycle Re-Entry Enhances Neuropathological Features in AppNLF Knock-In Mice.Journal of Alzheimer's disease : JAD · 2021Article
- Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development.Aging and disease · 2020Review
- The Pathway Coexpression Network: Revealing pathway relationships.PLoS computational biology · 2018Article
- The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.Hormones and behavior · 2015Review
- A Unified Hypothesis of Early- and Late-Onset Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2015Review
- Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg-AD mouse model and Alzheimer's disease patients.Journal of Alzheimer's disease : JAD · 2015Article
- Article
- MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau-phosphorylation, and apoptosis in postmitotic neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Article
- Discrete phosphorylated retinoblastoma protein isoform expression in mouse tooth development.Journal of molecular histology · 2012Article
- The cell cycle regulator phosphorylated retinoblastoma protein is associated with tau pathology in several tauopathies.Journal of neuropathology and experimental neurology · 2011Article
- p38 phosphorylates Rb on Ser567 by a novel, cell cycle-independent mechanism that triggers Rb-Hdm2 interaction and apoptosis.Oncogene · 2011Article
- Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease.Cellular and molecular life sciences : CMLS · 2010Article
- S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons.Brain : a journal of neurology · 2010Article
- Pathological implications of cell cycle re-entry in Alzheimer disease.Expert reviews in molecular medicine · 2010Review
- The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse.The American journal of pathology · 2009Article
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Authors and funding
15 authors.
Funding
Abstract
The re-expression of multiple cell cycle markers representing various cell cycle phases in postmitotic pyramidal neurons suggests that neurons in Alzheimer disease (AD) attempt to re-enter the cell cycle. Entry into the cell cycle requires activation of G1 to S phase cell cycle proteins, among which retinoblastoma protein (pRb) is a key regulator. pRb inhibits the transcription of cell cycle proteins in the nucleus of healthy cells by interaction and consequent blocking of the active site of E2F, dependent upon the phosphate stoichiometry and combination of the locations of their 16 potential phosphorylation sites on pRb. Therefore, to determine whether pRb is involved in the aberrant cell cycle phenotype in AD neurons, a systematic immunocytochemical evaluation of the phosphorylation status of pRb protein using antibodies specific for multiple phosphorylation sites (i.e., pSpT249/252, pS612, pS795, pS807, pS811 and pT821) was carried out in the hippocampal regions of brains from AD patients. Increased levels of phospho-pRb (ppRb) for all these phosphorylation sites were noted in the brains of AD patients as compared to control cases. More importantly, redistribution of ppRb from the nucleus to the cytoplasm of susceptible neurons, with significant localization in neurofibrillary tangles and neuritic plaques, was observed. Additional studies revealed extensive co-localization between phospho-p38 and ppRb, implicating that p38 activation may contribute to cell cycle abnormalities through pRb phosphorylation. Taken together, these data supports the concept of neuronal cell cycle re-entry in AD and indicates a crucial role for pRb in this process.
Indexed as
Identifiers
18784806PMC2480556W1753657787What OpenQuestion holds
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.