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- Title
Cycling at the interface between neurodevelopment and neurodegeneration.
- Authors
Nguyen, M.D.; Mushynski, W.E.; Julien, J.-P.
- Abstract
The discovery of cell cycle regulators has directed cell research into uncharted territory. In dividing cells, cell cycleassociated protein kinases, which are referred to as cyclindependent-kinases (Cdks), regulate proliferation, differentiation, senescence and apoptosis. In contrast, all Cdks in postmitotic neurons, with the notable exception of Cdk5, are silenced. Surprisingly, misregulation of Cdks occurs in neurons in a wide diversity of neurological disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Ectopic expression of these proteins in neurons potently induces cell death with hallmarks of apoptosis. Deregulation of the unique, cell cycle-unrelated Cdk5 by its truncated co-activator, p25 and p29, contributes to neurodegeneration by altering the phosphorylation state of non-membrane-associated proteins and possibly through the induction of cell cycle proteins. On the other hand, cycling Calks such as Cdk2, Cdk4 and Cdk6, initiate death pathways by derepressing E2F-1/Rb-dependent transcription at the neuronal G1/S checkpoint. Thus, Cdk5 and cycling Cdks may have little in common in the healthy CNS, but they likely conspire in leading neurons to their demise.
- Subjects
CYCLIN-dependent kinases; CELL cycle; NEURONS
- Publication
Cell Death & Differentiation, 2002, Vol 9, Issue 12, p1294
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4401108