Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease

Hyoung gon Lee*, Gemma Casadesus, Xiongwei Zhu, Rudy J. Castellani, Andrew McShea, George Perry, Robert B. Petersen, Vladan Bajic, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

118 Scopus citations


As one of the earliest pathologic changes, the aberrant re-expression of many cell cycle-related proteins and inappropriate cell cycle control in specific vulnerable neuronal populations in Alzheimer's disease (AD) is emerging as an important component in the pathogenesis leading to AD and other neurodegenerative diseases. These events are clearly representative of a true cell cycle, rather than epiphenomena of other processes since, in AD and other neurodegenerative diseases, there is a true mitotic alteration that leads to DNA replication. While the exact role of cell cycle re-entry is unclear, recent studies using cell culture and animal models strongly support the notion that the dysregulation of cell cycle in neurons leads to the development of AD-related pathology such as hyperphosphorylation of tau and amyloid-β deposition and ultimately causes neuronal cell death. Importantly, cell cycle re-entry is also evident in mutant amyloid-β precursor protein and tau transgenic mice and, as in human disease, occurs prior to the development of the pathological hallmarks, neurofibrillary tangles and amyloid-β plaques. Therefore, the study of aberrant cell cycle regulation in model systems, both cellular and animal, may provide extremely important insights into the pathogenesis of AD and also serve as a means to test novel therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
JournalNeurochemistry International
Issue number2
StatePublished - Feb 2009


  • Alzheimer's disease
  • Amyloid-β
  • Cell cycle
  • Neurodegeneration
  • Tau phosphorylation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology


Dive into the research topics of 'Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this