Research Paper Volume 1, Issue 4 pp 382—388
Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease
- 1 Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
- 2 National Centre for Biomedical Engineering and Science, National University of Ireland Galway, Galway, Ireland
- 3 Departamento de Fisiología, Facultad de Medicina, Avda. Blasco Ibáñez 15, 46010 Valencia, Spain
- 4 Institute of Biomedical Research, Galenika a.d., 11000 Belgrade, Serbia
- 5 Department of Pathology, University of Maryland, Baltimore, MD 21250, USA
- 6 College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249, USA
Received: April 2, 2009 Accepted: April 23, 2009 Published: April 23, 2009
https://doi.org/10.18632/aging.100044How to Cite
Abstract
Aberrant neuronal re-entry into the cell cycle is emerging as a potential pathological mechanism in Alzheimer disease (AD). However, while cyclins, cyclin dependent kinases (CDKs), and other mitotic factors are ectopically expressed in neurons, many of these proteins are also involved in other pathological and physiological processes, generating continued debate on whether such markers are truly indicative of a bona fide cell cycle process. To address this issue, here we analyzed one of the minichromosome maintenance (Mcm) proteins that plays a role in DNA replication and becomes phosphorylated by the S-phase promoting CDKs and Cdc7 during DNA synthesis. We found phosphorylated Mcm2 (pMcm2) markedly associated with neurofibrillary tangles, neuropil threads, and dystrophic neurites in AD but not in aged-matched controls. These data not only provide further evidence for cell cycle aberrations in AD, but the cytoplasmic, rather than nuclear, localization of pMcm2 suggests an abnormal cellular distribution of this important replication factor in AD that may explain resultant cell cycle stasis and consequent neuronal degeneration.