Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease.

Authors: Bonda, DJ  Evans, TA  Santocanale, C  Llosa, JC  Vina, J  Bajic, V  Castellani, RJ  Siedlak, SL  Perry, G  Smith, MA  Lee, HG 
Citation: Bonda DJ, etal., Aging (Albany NY). 2009 Apr;1(4):382-8.
Pubmed: (View Article at PubMed) PMID:19946466
DOI: Full-text: DOI:10.18632/aging.100044

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.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 10412048
Created: 2015-11-12
Species: All species
Last Modified: 2015-11-12
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.