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The effect of manganese speciation on its mitochondrial toxicity: implications for neurotoxicity mechanism of the manganese

Grant number: 09/16018-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2010
Effective date (End): October 31, 2010
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Nadja Cristhina de Souza Pinto
Grantee:Raúl Bonne Hernández
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Manganese (Mn) is essential for living organisms, playing an important role in nervous system function, bone mineralization, protein and energy metabolism, metabolic regulation and cellular protection. However, chronic exposure for this metal, mainly during early life stages, can lead to toxicity, with the central nervous system as the primary target. Indeed, Mn toxicity has been associated with Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, schizophrenia, and autism. Because the average life span of the human population has increased significantly in the last century, and several of these diseases are associated with aging, the cost of public health programs has increased as well. Numerous hypotheses have been proposed to explain Mn neurotoxicity, and mitochondrial dysfunction and impaired energy metabolism have been proposed to play a significant role. However, at present little experimental data support this relationship and the role the Mn speciation for Mn mitochondrial toxicity and neurotoxicity is still unclear. We hypothesize that chronic exposure to Mn species induces differential mitochondrial alterations, energy metabolism disruption, followed by oxidative stress, ultimately leading to apoptotic and/or necrosis events. Thus, we propose to study the role of mitochondrial impairment in Mn neurotoxicity by biochemical and toxicogenomics approaches. In addition, since manganese can be found in different bioavailable species, we propose to investigate the specific effects of such species on mitochondrial impairment. The data generated by this project will improve the knowledge about the mechanisms of toxicity of the Mn, and may help in devising better therapeutic alternative for Mn poisoning. (AU)

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)
HERNÁNDEZ‚ RB; FARINA‚ M.; ESPÓSITO‚ BP; SOUZA-PINTO‚ NC; BARBOSA JR‚ F.; SUÑOL‚ C. Mechanisms of Manganese-Induced Neurotoxicity in Primary Neuronal Cultures: The Role of Manganese Speciation and Cell Type. TOXICOLOGICAL SCIENCES, v. 124, n. 2, p. 414-423, 2011. Web of Science Citations: 38.

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