Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?

Bioscience Hypotheses
V P BajićMark A Smith

Abstract

Chromosomal involvement is a legitimate, yet not well understood, feature of Alzheimer disease (AD). Firstly, AD affects more women than men. Secondly, the amyloid-β protein precursor genetic mutations, responsible for a cohort of familial AD cases, reside on chromosome 21, the same chromosome responsible for the developmental disorder Down's syndrome. Thirdly, lymphocytes from AD patients display a novel chromosomal phenotype, namely premature centromere separation (PCS). Other documented morphological phenomena associated with AD include the occurrence of micronuclei, aneuploidy, binucleation, telomere instability, and cell cycle re-entry protein expression. Based on these events, here we present a novel hypothesis that the time dimension of cell cycle re-entry in AD is highly regulated by centromere cohesion dynamics. In view of the fact that neurons can re-enter the cell division cycle, our hypothesis predicts that alterations in the signaling pathway leading to premature cell death in neurons is a consequence of altered regulation of the separation of centromeres as a function of time. It is well known that centromeres in the metaphase-anaphase transition separate in a non-random, sequential order. This sequence has been s...Continue Reading

References

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May 8, 2004·Experimental Gerontology·Biljana Spremo-PotparevicVladan Bajic
Jul 13, 2004·Nature Cell Biology·Tatsuo FukagawaMitsuo Oshimura
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Jul 16, 2008·Journal of Neurochemistry·Biljana Spremo-PotparevićVladan Bajić

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