Content area
Full text
About the Authors:
Mariana Dias Castela de Carvalho
Affiliation: Bioinformatics and Computational Biology Group, Department of Genetics and Molecular Biology, Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil
Joelma Freire De Mesquita
* E-mail: [email protected]
Affiliation: Bioinformatics and Computational Biology Group, Department of Genetics and Molecular Biology, Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil
Introduction
Although aging is a multifactorial process, there is significant evidence that shows that oxidative stress is one of the main factors that influences cellular longevity. Interest in the factors that determine longevity has grown recently because the life expectancy of the world population is increasing. Additionally, in many countries, the main causes of death are currently comorbidities connected to age and oxidative stress.
Superoxide dismutases (SODs) protect against oxidative stress and have three forms: Cu-Zn SOD (SOD1), located in the cytosol; Mn-SOD (SOD2), located in the mitochondrial matrix; and extracellular SOD (SOD3) [1]. The disproportionate rate of intrauterine death and early fatality in Mn-SOD knock-out animals demonstrated the importance of Mn-SOD, rather than SOD1 and SOD3, in foetal development. [1].
The first 24 amino acids of Mn-SOD are the mitochondrial targeting sequence (MTS), which guides and docks the Mn-SOD protein to mitochondria. [1].
Polymorphisms in SOD2 have been associated with the development of neurodegenerative diseases, such as Alzheimer’s [2](A16V) and Parkinson’s disease [3] [4] [1] (A16V and I82T), as well as psychiatric disorders, such as schizophrenia [5], depression [6]and bipolar disorder [7]. Similarly, clinical trials showed improvement in symptoms in response to treatment with the glutathione precursor NAC in patients with schizophrenia and bipolar disorder [8] [9], suggesting that defects in the oxidative stress pathway may contribute to the pathogenesis of various diseases and symptoms. Studies suggest that the effects of all natural variants may primarily reflect functional polymorphism of mitochondrial transport of human MnSOD. As oxidative damage is believed to be an important factor in the pathogenesis of all of these diseases, all of the known variants could possibly contribute to the associated risks. The knowledge of their molecular basis facilitates the diagnosis and design of new drugs.
In this study, we collected the natural variants of SOD2 for in silico analysis, which can determine whether these variants influence the protein’s three-dimensional...