The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

Figure 5

Target-based drugs against T. cruzi and SIRT1 therapy. Drugs are being developed against specific T. cruzi pathways, and they are shown in the figure. Both the parasite and the mammalian host possess sirtuins; therefore, target-based drugs have been tested against the parasite sirtuins, and antioxidant therapies have been developed to improve the activity of mammalian SIRT1, either by using resveratrol antioxidant or the SRT1720 agonist, which is able to activate SIRT1, which in turn can activate PGC-1α to promote mitochondrial biogenesis and OXPHOS function and improve heart function through the transcription factors NRF1 and NRF2. Also, PGC-1α is a coactivator for NFE2L2, which can activate the antioxidant system. On the other hand, activated SIRT1 can inhibit the activity of transcription factor NF-κB, which leads to a decrease of proinflammatory cytokine production, and also can inhibit the activity of FAK.