RGD Reference Report - Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease. - Rat Genome Database

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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.
RGD ID: 10412048
Pubmed: PMID:19946466   (View Abstract at PubMed)
PMCID: PMC2783633   (View Article at PubMed Central)
DOI: DOI:10.18632/aging.100044   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IDA 10412048 RGD 
Alzheimer's disease  ISOMCM2 (Homo sapiens)10412048; 10412048 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mcm2  (minichromosome maintenance complex component 2)

Genes (Mus musculus)
Mcm2  (minichromosome maintenance complex component 2)

Genes (Homo sapiens)
MCM2  (minichromosome maintenance complex component 2)


Additional Information