Title:Nuclear Factor Erythroid 2 - Related Factor 2 Signaling in Parkinson Disease: A Promising Multi Therapeutic Target Against Oxidative Stress, Neuroinflammation and Cell Death
VOLUME: 11 ISSUE: 8
Author(s):Hemant Kumar, Sushruta Koppula, In-Su Kim, Sandeep Vasant More, Byung-Wook Kim and Dong-Kug Choi
Affiliation:Department of Biotechnology, Konkuk University, Chungju, 380-701, Korea.
Keywords:Antioxidant inflammation modulators, antioxidant response elements, apoptosis, nuclear factor erythroid 2-related
factor 2, neuroinflammation, oxidative stress, Parkinson’s disease, dopaminergic neurons, neurotransmitter, robust antioxidant.
Abstract:Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder with increased
oxidative stress as central component. Till date, treatments related to PD are based on restoring dopamine either by
targeting neurotransmitter and/or at receptor levels. These therapeutic approaches try to repair damage but do not address
the underlying processes such as oxidative stress and neuroinflammation that contribute to cell death. The central nervous
system maintains a robust antioxidant defense mechanism consisting of several cytoprotective genes and enzymes whose
expression is controlled by antioxidant response element (ARE) which further depends on activation of nuclear factor
erythroid 2-related factor 2 (Nrf2). In response to oxidative or electrophilic stress transcription factor Nrf2 binds to ARE
and rescues the cells from oxidative stress and neuroinflammation. Recently, Nrf2 has been utilized as a drug target and
some agents are currently under clinical trial. Owing to the potential role of Nrf2 in counteracting oxidative stress and
neuroinflammation seen in PD, here we have focused on the molecular mechanism of the Nrf2/ARE antioxidant defense
pathway in PD. Further, we also summarize published reports on the potential inducers of Nrf2 that demonstrate
neuroprotective effects in experimental models of PD with possible future strategies to increase the transcriptional level of
Nrf2 as a therapeutic strategy to provide neuroprotection of damaged dopaminergic neurons in PD.
