The cell cycle regulator phosphorylated retinoblastoma protein is associated with tau pathology in several tauopathies

Jeremy G. Stone, Sandra L. Siedlak, Massimo Tabaton, Asao Hirano, Rudy J. Castellani, Corrado Santocanale, George Perry, Mark A. Smith, Xiongwei Zhu, Hyoung Gon Lee

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Retinoblastoma protein (pRb) is a ubiquitous 928-amino acid cell cycle regulatory molecule with diverse biologic activities. One criticalfunction of pRb is the control of the G1-to-S phase checkpoint of the cell cycle. In the hypophosphorylated state, pRb suppresses the activity of E2F transcription factors thereby inhibiting transcription ofcell 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 cellcycle 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 (3cases 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 cycleprogression in neurodegenerative diseases, particularly tauopathies, and suggest a novel target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)578-587
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume70
Issue number7
DOIs
Publication statusPublished - Jul 1 2011

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Keywords

  • Dementia pugilistica
  • Neurodegeneration with brain iron accumulation type 1
  • Neurofibrillary tangles
  • Pick disease
  • Progressive supranuclear palsy
  • Retinoblastoma protein
  • Subacute sclerosing panencephalitis
  • Tau pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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