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Review
. 2019 Jun 29;20(13):3208.
doi: 10.3390/ijms20133208.

Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

Fabiane Valentini Francisqueti-Ferron  1 , Artur Junio Togneri Ferron  2 , Jéssica Leite Garcia  2 , Carol Cristina Vágula de Almeida Silva  2 , Mariane Róvero Costa  2 , Cristina Schmitt Gregolin  2 , Fernando Moreto  2 , Ana Lúcia A Ferreira  2 , Igor Otávio Minatel  3 , Camila Renata Correa  2
Affiliations
Review

Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

Fabiane Valentini Francisqueti-Ferron et al. Int J Mol Sci. .

Abstract

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

Keywords: Nrf2; age-related disorders; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
In cells under homeostatic conditions, cytosolic transcription factor Nrf2 is kept at low levels by proteasomal degradation trigged by the Keap1 protein complex. When cells are under oxidative stress, free radicals induce the Nrf2 to release from Keap1, escaping from proteasomal degradation, and it translocates to the nucleus. In the nucleus, Nfr2 binds to the ARE and starts the transcription of antioxidant enzymes as heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamine-cysteine ligase (GCL), and glutathione synthetase (GS). These enzymes act by reducing the cell oxidative stress and free radicals. Black arrows indicate pathways activation; Red T-bars indicate blocking processes.
Figure 2
Figure 2
Nrf2 effect on age-related disorders. ROS—reactive oxygen species; RNS—reactive nitrogen species; AGE—advanced glycation end products; ALE—advanced lipoxidation end products; HO-1—heme oxygenase-1; DJ-1—protein deglycase.
See this image and copyright information in PMC

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