A Systematic Analysis of the Human Nrf2 Network

Ponsford, Amy Hine (2022) A Systematic Analysis of the Human Nrf2 Network. Doctoral thesis, UIN SAIZU Purwokeerto.

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Abstract

Nrf2 is the main transcriptional controller of cellular oxidative stress responses. This is achieved by driving the transcription of a battery of cytoprotective genes that possess a characteristic Antioxidant Response Element (ARE) sequence in their upstream promoter regions. As such, the Nrf2 signalling pathway plays a vital role in health, aging and disease. Defects in Nrf2 activity can lead to impaired mitochondrial function and reduced protection against free radical damage. Over time these effects contribute to common age-related conditions including cardiovascular disease, neurodegeneration and chronic inflammatory conditions. Despite the well-characterised cytoprotective role of Nrf2, inappropriate over or under activation of Nrf2 signalling can also be detrimental. It is therefore important to develop a better understanding of how Nrf2 signalling networks may be regulated. For that reason, the primary aim of this project was to provide a better systems level contextual understanding of Nrf2 signalling in human cells, by generating an improved high-density experimentally defined human Nrf2-centric protein-protein interaction network

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