Antioxidant Improvements by Nrf2 and PPAR Gamma Activation in Cardiovascular and Neurodegenerative Diseases

Dear Colleagues,

Mammalian cells have evolved a unique strategy to protect themselves against oxidative damage induced by reactive oxygen species (ROS). The transcription factors nuclear factor erythroid 2-related factor 2  (Nrf2) and nuclear factor peroxisome proliferator-activated receptor γ (PPARγ) have been shown to play key roles in establishing this cellular antioxidative defense system. (...to play key roles in maintaining cellular redox homeostasis via the activation of antioxidant defense systems).

Nrf2 (or NFE2L2) functions as a target nuclear receptor against oxidative stress (...functions as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress) and is a key factor in redox regulation in hypertension, cardiovascular, and neurodegenerative diseases. The Keap1-Nrf2-ARE (antioxidant response element ) system regulates many detoxifying and antioxidant enzymes in cells after the exposure to reactive oxygen species and electrophiles. Activation of Nrf2/ARE signaling is differentially regulated during acute and chronic stress.

PPARγ is a nuclear receptor playing an important role in the management of cardiovascular diseases, hypertension, and metabolic syndrome. PPARγ targets genes with peroxisome proliferator response element (PPRE), leading to the identification of several genes involved in lipid metabolism or oxidative stress. PPARγ stimulation is triggered by endogenous and exogenous ligands–agonists, and it is involved in the activation of several cellular signaling pathways involved in oxidative stress response, such as the PI3K/Akt/NOS pathway.

Nrf2 and PPARγ pathways seem to be connected by a positive feedback loop, which maintains the expression of both transcription factors and their target antioxidant genes in a simultaneous manner. Moreover, Nrf2 and PPARγ are linked together through effects of their several activators. The importance of  Nrf2/ARE and PPARγ/PPRE pathways is supported by the fact both play an important role in the control of cardiovascular and neurodegenerative diseases.

Dr. Ima Dovinová
Prof. Dr. Julie Y.H. Chan
Dr. Guliz Armagan
Dr. Miroslav Barančík
Guest Editors

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• Oxidative stress
• Nrf2
• PPARγ
• Antioxidants
• Redox regulation
• Cardiovascular disease
• Neurodegenerative disease