4 research outputs found
Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease
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
Evidence for the progression through s-phase in the ectopic cell cycle re-entry of neurons in alzheimer disease
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