Molecular Mechanisms of Neurodegeneration Involving the Effect of Environmental Pollutants on Dna Repair Enzymes

Several works suggest that oxidative DNA damage and alterations of DNA repair enzymes in neuronal cells contribute to the onset of neurodegenerative diseases and neuronal cancer. Cadmium is a common environmental pollutant able to induce oxidative stress leading to the activation of neuronal death pathways and it is also able to inhibit specific DNA repair enzymes of the BER (Base Excision Repair) pathway, the principle cellular way for repairing oxidative DNA damages. One of these enzymes is APE1, a small multifunctional protein that, besides its key role in the BER pathway, has also a redox function important for the control of the intracellular redox state and for the regulation of gene expression. Furthermore, some papers report its contribution both in neuronal protection from oxidative damage and in the development of neurodegenerative diseases. However, the possible involvement of APE1 and of the BER pathway in cadmiuminduced neuronal cell damage is still unknown. Index Terms — MINA, environmental pollutants, neurodegeneration, cadmium _____________________________________________________________________