The most common cause of dementia in the elderly is Alzheimer disease (AD). In Europe, AD is a leading cause of death. The prevalence of this disease in developed countries is increasing because of very significant shifts in life expectancy and demographic parameters. AD is characterized by progressive cognitive impairment, resulting from dysfunction and degeneration of neurons in the limbic and cortical regions of the brain. Two prominent abnormalities in the affected brain regions are extracellular deposits of beta-amyloid, and intracellular aggregates of tau protein in neurofibrillary tangles. The role of these features in AD pathogenesis and progression is not yet completely elucidated. Research over the last decade has revealed that the activation of cell cycle machinery in postmitotic neurons is one of the earliest events in neuronal degeneration in AD. Here we summarize evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Immortalized lymphocytes from AD patients have show an enhanced rate of proliferation associated with G1/S regulatory failure induced by alterations in the cyclin/CDK/pRb/E2F pathway. In addition, these cells have a higher resistance to serum deprivation-induced apoptosis. These neoplastic-like features, cell cycle dysfunction and impaired apoptosis can be considered systemic manifestations of AD disease.
- MeSH
- Alzheimerova nemoc diagnóza krev patofyziologie MeSH
- buněčný cyklus genetika imunologie účinky léků MeSH
- financování organizované MeSH
- inhibitor p21 cyklin-dependentní kinasy izolace a purifikace MeSH
- inhibitor p27 cyklin-dependentní kinasy izolace a purifikace MeSH
- kalmodulin diagnostické užití MeSH
- lidé MeSH
- lymfocyty cytologie patologie účinky léků MeSH
- modely u zvířat MeSH
- proliferace buněk účinky léků MeSH
- statistika jako téma MeSH
- viabilita buněk genetika účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH