Effects of metalloenzyme superoxide dismutase expression in the generation of reactive oxygen species in cultured mammalian cells and in motor neurons

Abstract

Many processes involving aggregation and function of metalloenzyme Cu, Zn-Superoxide Dismutase (SOD1 or Cu, Zn-SOD) as peroxidase are still in full debate in the literature after more than 40 years of its discovery and characterization. In this area of research the role of mutations in the enzyme linked to familial cases of the disease Amyotrophic Lateral Sclerosis (ALS), a disease that particularly affects motor neurons, begins to be elucidated recently, where it was known that the observed protein aggregation type and severity of disease depends the type of mutation in SOD1. We know very little about how the SOD1 without mutations, would be involved in sporadic cases of ALS (most common). Therefore in this research project we intend to study regularly the SOD1wt behave in primary cultured motor neurons (mouse) and in immortalized cells in culture, studying the overexpression of SOD1 in the aspects of homeostasis of reactive oxygen species (ROS), causing differences in viability, mitochondrial membrane integrity and aggregation of SOD and other cytoskeletal proteins. This overexpression of SOD1 in mammalian cells aims to mimic a biochemical situation that would lead to symptoms in an animal model of ALS. (AU)