The cell cycle regulator phosphorylated retinoblastoma protein is associated with tau pathology in several tauopathies
Stone, Jeremy G. Siedlak, Sandra L. Tabaton, Massimo Hirano, Asao Castellani, Rudy J. Santocanale, Corrado Perry, George Smith, Mark A. Zhu, Xiongwei Lee, Hyoung-gon
Stone, Jeremy G.
Siedlak, Sandra L.
Tabaton, Massimo
Hirano, Asao
Castellani, Rudy J.
Santocanale, Corrado
Perry, George
Smith, Mark A.
Zhu, Xiongwei
Lee, Hyoung-gon
Identifiers
http://hdl.handle.net/10379/14027
https://doi.org/10.13025/28649
https://doi.org/10.13025/28649
Repository DOI
Publication Date
2011-07-01
Keywords
dementia pugilistica, neurodegeneration with brain iron accumulation type 1, neurofibrillary tangles, pick disease, progressive supranuclear palsy, retinoblastoma protein, subacute sclerosing panencephalitis, tau pathology, progressive supranuclear palsy, microtubule-associated protein, alzheimers-disease, s-phase, prb phosphorylation, 2-hit hypothesis, oxidative stress, expression, kinase, activation
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Article
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Stone, Jeremy G. Siedlak, Sandra L.; Tabaton, Massimo; Hirano, Asao; Castellani, Rudy J.; Santocanale, Corrado; Perry, George; Smith, Mark A.; Zhu, Xiongwei; Lee, Hyoung-gon (2011). The cell cycle regulator phosphorylated retinoblastoma protein is associated with tau pathology in several tauopathies. Journal of Neuropathology & Experimental Neurology 70 (7), 578-587
Abstract
Retinoblastoma protein (pRb) is a ubiquitous 928-amino acid cell cycle regulatory molecule with diverse biologic activities. One critical function of pRb is the control of the G(1)-to-S phase checkpoint of the cell cycle. In the hypophosphorylated state, pRb suppresses the activity of E2F transcription factors thereby inhibiting transcription of cell cycle-promoting genes. On phosphorylation, primarily by cyclin-dependent kinases, phosphorylated pRb dissociates from E2F and permits cell cycle progression. We previously found phosphorylated pRb to be intimately associated with hyperphosphorylated tau-containing neurofibrillary tangles of Alzheimer disease (AD), the pathogenesis of which is believed to involve dysregulation of the cell cycle and marked neuronal death. Here, we used immunohistochemistry to investigate the presence of phosphorylated pRb in other distinct neurodegenerative diseases that share the common characteristic of hyperphosphorylated tau pathology and neuronal loss with AD. We found colocalized labeling of tau pathology and phosphorylated pRb in Pick disease and progressive supranuclear palsy (3 cases each), neurodegeneration with brain iron accumulation type 1 (2 cases), and Parkinson-amyotrophic lateral sclerosis of Guam, subacute sclerosing panencephalitis, frontotemporal dementia and Parkinsonism linked to chromosome 17, and dementia pugilistica (1 case each). These observations further implicate aberrant neuronal cell cycle progression in neurodegenerative diseases, particularly tauopathies, and suggest a novel target for therapeutic intervention.
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Publisher
Oxford University Press (OUP)
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Attribution-NonCommercial-NoDerivs 3.0 Ireland