|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||March 01, 2016|
|Effective date (End):||February 29, 2020|
|Field of knowledge:||Biological Sciences - Biochemistry - Metabolism and Bioenergetics|
|Principal researcher:||Roger Frigério Castilho|
|Home Institution:||Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil|
The nicotinamide nucleotide transhydrogenase (NNT) is a transmembrane protein located in the inner mitochondrial membrane that catalyzes the reduction of NADP+ by NADH producing NADPH and NAD+, coupled to the transport of protons from the intermembrane space to the mitochondrial matrix. This protein is expressed in all mammalian and its function is related to the maintenance of mitochondrial and cellular homeostatic mechanisms, such as reactive oxygen species metabolism by glutathione reductase/peroxidase and thioredoxin/peroxiredoxin systems. Pathological changes like familial deficiency of glucocorticoids and mineralocorticoids in humans are linked to NNT deficiency. NNT activity also has relevance in the metabolism and proliferation of tumor cells. While there have been advances in research on the role of NNT in cellular metabolism, details of its physiology and its influence in pathophysiological states have yet to be elucidated. Thus, this project aims to characterize the NNT expression and activity in mouse brains, assess the role of NNT in reactive oxygen species release by brain mitochondria and finally, investigate the importance of NNT in an experimental model for Parkinson's disease. For this purpose, comparative studies will be conducted using C57BL/6 mice with a spontaneous mutation in the NNT gene (C57Unib.B6-NNT-/-) which results in absence of protein expression, and congenic mice with normal NNT expression (C57Unib.B6-NNT+/+). Colonies of these mice are already established in our laboratory and are a suitable model for studying pathophysiological aspects of NNT.