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Review
. 2004 Oct 20;24(42):9232-9.
doi: 10.1523/JNEUROSCI.3347-04.2004.

Divide and die: cell cycle events as triggers of nerve cell death

Karl Herrup  1 , Rachael Neve, Susan L Ackerman, Agata Copani
Affiliations
Review

Divide and die: cell cycle events as triggers of nerve cell death

Karl Herrup et al. J Neurosci. .
No abstract available

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Figures

Figure 1.
Figure 1.
Cell cycle events in hippocampal pyramidal neurons of human and mouse. A, A neuron in the CA1 hippocampal region of a patient who died with Alzheimer's disease. The neuron indicated by the black arrow is immunopositive for the PCNA protein, an S-phase marker (from Busser et al., 1998). B, A CA3 area pyramidal cell from an Alzheimer's patient hybridized with a unique genomic probe from chromosome 11. Note the four spots of hybridization (white arrows) indicating the full replication of this portion of the genome (from Yang et al., 2001). C, The CA1 region of an R1.40 transgenic mouse stained with an antibody to cyclin A (green) and counterstained with propidium iodide (red). Note that the three neurons are immunopositive for this S-phase marker (Y. Yang, B. T. Lamb, and K. Herrup, unpublished observations).
Figure 2.
Figure 2.
A noncanonical pathway of DNA replication is mediated by polβ and is causally related to neuronal death. In dividing cells (top), DNA replication (yellow strand) is accomplished by DNA polα and polδ/ϵ, which follow one another in the elongation of the short RNA primer synthesized by the primase (red). In neurons challenged with Aβ (bottom), DNA replication (purple strand) is performed by polβ that substitutes for polα. The error-prone activity of polβ might generate DNA damage, eventually leading to cell death. Some DNA replication is possibly mediated by polδ but does not contribute to neuronal death (Copani et al., 2002).
Figure 3.
Figure 3.
The involvement of DNA replication in neuronal death depends on the type of insult and the susceptibility of neurons. A, A susceptible neuron (smaller circle) in the presence of a severe insult (thick vertical arrow), which possibly causes extensive DNA damage, dies without the contribution of de novo DNA synthesis. B, In a less vulnerable neuron (bigger circle) exposed to other types of insults, including Aβ or mild oxidative stress, de novo DNA synthesis becomes essential for neuronal death.
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