Molecular Connections between DNA Replication and Cell Death in β-Amyloid-Treated Neurons.

ABSTRACT:

Background

Ectopic cell cycle reactivation in neurons is associated with neuronal death in Alzheimer's disease. In cultured rodent neurons, synthetic β-amyloid (Aβ) reproduces the neuronal cell cycle re-entry observed in the Alzheimer's brain, and blockade of the cycle prevents Aβ-induced neurodegeneration. DNA polymerase-β, whose expression is induced by Aβ, is responsible for the DNA replication process that ultimately leads to neuronal death, but the molecular mechanism(s) linking DNA replication to neuronal apoptosis are presently unknown.

Aim

To explore the role of a conserved checkpoint pathway started by DNA replication stress, namely the ATM-ATR/Claspin/Chk-1 pathway, in switching the neuronal response from DNA replication to apoptosis.

Methods

Experiments wer

SUBMITTER: Caraci F 

PROVIDER: S-EPMC10514525 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature