Erratic expression of DNA polymerases by β‐amyloid causes neuronal death

Abstract

SPECIFIC AIMSReactivation of a quiescent cell cycle machinery takes place in many neurodegenerative conditions, including Alzheimer’s disease (AD). Neurons of the AD brain undergo DNA replication, as do cortical neurons challenged with β-amyloid peptide (βAP). The evidence that DNA replication is required for neuronal apoptosis induced by βAP suggests that the molecular machinery carrying out DNA replication in neurons is at the origin of apoptotic degeneration. We sought to investigate the repertoire of DNA polymerases expressed in βAP-treated neurons and their specific role in DNA synthesis and apoptosis.PRINCIPAL FINDINGS1. Cell cycle-dependent expression of DNA polymerases in βAP-treated neuronsTo investigate the repertoire of enzymes that allow neurons to start DNA replication in response to βAP, we examined whether βAP-treated neurons express DNA polymerases, known to carry out DNA replication in proliferating cells. De novo DNA synthesis is accomplished by the coordinated activity of DNA polymerase...