Current Drug Targets - CNS & Neurological Disorders

Stephen D. Skaper
Department of Pharmaceutical and Pharmacological Sciences
University of Padova
Padova
Italy

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The Expression of Cell Cycle Proteins in Neurons and its Relevance for Alzheimers Disease

Author(s): Uwe Ueberham, Thomas Arendt.

Abstract:

Alzheimers disease is a chronic neurodegenerative disorder characterised by typical pathological hallmarks such as amyloid deposition, neurofibrillary tangles and disturbances in the expression of various cell cycle proteins. A current pathogenetic hypothesis suggests that neurons, forced by external and internal factors, leave the differentiated G0 phase and re-enter the cell cycle. This process results in neuronal dedifferentiation and apoptosis and might contribute to an increased phosphorylation of the tau protein. There are a number of reports, however, describing the expression of cell cycle proteins in rodent or human brain under normal non-disease conditions. This might indicate that cell cycle expression of proteins in neurons is of physiological rather than pathophysiological relevance. Therefore, it needs to be carefully analysed whether the expression of cell cycle regulators such as cyclin-dependent kinases, cyclins or cyclin-dependent kinase inhibitors in neurons is a pathological hallmark that allows to discriminate between normal and disease condition. Here we attempt to summarise recent evidence for a dysfunction of cell cycle regulators in Alzheimer´s disease, considering the potential functions of these molecules beyond cell cycle regulation.

Keywords: alzheimers disease, cell cycle, cyclin, cyclin-dependent kinase, apoptosis, dna replication, dna repair

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Article Details

VOLUME: 4
ISSUE: 3
Year: 2005
Page: [293 - 306]
Pages: 14
DOI: 10.2174/1568007054038175
Price: $58