Cyclin C expression is involved in the pathogenesis of Alzheimer's disease.
The expression of different cell cycle proteins in terminally differentiated neurons apparently precedes cell death or contributes to pathogenetic progression of Alzheimer's disease (AD). Cyclins and cyclin-dependent kinases (Cdks), physiologically involved in mitotic processes of proliferating cells, are elevated in neurons prone to dedifferentiation and degeneration. Previously, it was shown that even inhibitors of the Cdks as p16(INK4a), p18(INK4c) or p27(KIP1) are expressed in neurons of AD patients, indicating a rather complete involvement of cell cycle machinery in affected neurons. The aim of this study was to examine the involvement of the non-classical cyclin C in the pathogenetic process of AD. A marked elevated immunoreactivity of cyclin C was found both in neurons and astrocytes in AD. Increased levels of cyclin C RNA were detected by ribonuclease protection assay (RPA) in severe AD cases. Colocalization of cyclin C and its preferred binding partner, Cdk8, was only observed in astrocytes but not in neurons. The present observations suggest different cellular functions of cyclin C in neurons and astrocytes in AD.
Ueberham
Uwe
U
Department of Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109, Leipzig, Germany. uebu@medizin.uni-leipzig.de
Hessel
Annett
A
Arendt
Thomas
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001923:Brain Chemistry; D016022:Case-Control Studies; D056745:Cyclin C; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D016213:Cyclins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism*; D014018:Tissue Distribution
C503674:CCNC protein, human; D056745:Cyclin C; D016213:Cyclins; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases