The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated
damage in cancers and neurodegenerative diseases
#MMPMID28510041
Deshmukh P
; Unni S
; Krishnappa G
; Padmanabhan B
Biophys Rev
2017[Feb]; 9
(1
): 41-56
PMID28510041
show ga
The overproduction of reactive oxygen species (ROS) generates oxidative stress in
cells. Oxidative stress results in various pathophysiological conditions,
especially cancers and neurodegenerative diseases (NDD). The Keap1-Nrf2
[Kelch-like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2]
regulatory pathway plays a central role in protecting cells against oxidative and
xenobiotic stresses. The Nrf2 transcription factor activates the transcription of
several cytoprotective genes that have been implicated in protection from cancer
and NDD. The Keap1-Nrf2 system acts as a double-edged sword: Nrf2 activity
protects cells and makes the cell resistant to oxidative and electrophilic
stresses, whereas elevated Nrf2 activity helps in cancer cell survival and
proliferation. Several groups in the recent past, from both academics and
industry, have reported the potential role of Nrf2-mediated transcription to
protect from cancer and NDD, resulting from mechanisms involving xenobiotic and
oxidative stress. It suggests that the Keap1-Nrf2 system is a potential
therapeutic target to combat cancer and NDD by designing and developing
modulators (inhibitors/activators) for Nrf2 activation. Herein, we review and
discuss the recent advancement in the regulation of the Keap1-Nrf2 system, its
role under physiological and pathophysiological conditions including cancer and
NDD, and modulators design strategies for Nrf2 activation.
free
free
free
