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


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)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MATIAS, ANDREZA CANDIDO; MANIERI, TANIA MARIA; CERCHIARO, GISELLE. Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, . (12/01397-9)
MATIAS, A. C.; BIAZOLLA, G.; CERCHIARO, G.; KEPPLER, A. F.. alpha-Aryl-N-aryl nitrones: Synthesis and screening of a new scaffold for cellular protection against an oxidative toxic stimulus. Bioorganic & Medicinal Chemistry, v. 24, n. 2, p. 232-239, . (12/01397-9, 12/07717-5, 14/15534-3)
CERCHIARO, GISELLE; MANIERI, TANIA MARIA; BERTUCHI, FERNANDA RODRIGUES. Analytical methods for copper, zinc and iron quantification in mammalian cells. METALLOMICS, v. 5, n. 10, p. 1336-1345, . (12/01397-9)

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Filed patent(s) as a result of this research project

KIT PARA DETECÇÃO E QUANTIFICAÇÃO DE ATIVIDADE DA ENZIMA SUPERÓXIDO DISMUTASE (SOD) POR VIA COLORIMÉTRICA BR1020160032121 - Universidade Federal do ABC (UFABC) . Giselle Cerchiaro; Tânia Maria Manieri; Larissa Cristina Carvalho Do Lago; Samantha Dos Santos Cipriano; Bianca Dempsey Pinto - February 2016, 16