The expression of cell cycle proteins in neurons and its relevance for Alzheimer's disease.
Alzheimer's 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 G(0) phase and re-enter the cell cycle. This process results in neuronal de-differentiation 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.
Paul Flechsig Institute for Brain Research, Department of Neuroanatomy, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany. uebu@medizin.uni-leipzig.de
Uwe
U
Ueberham
Thomas
T
Arendt
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D004261:DNA Replication / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
D018797:Cell Cycle Proteins