Here, we review the preventive and protective effects of dietary Nrf2 activators against CNS diseases, including stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease.
By identifying the stress response strategies activated by Nrf2, we also highlight endogenous coping responses that might be therapeutically bolstered to treat PD.
DJ-1's effect on Nrf2 and subsequent effects on antioxidant responses may explain how DJ-1 affects the etiology of both cancer and PD, which are seemingly disparate disorders.
This complex α-synuclein-directed glial response highlights the importance of protein misfolding, oxidative stress and inflammation in PD and represents a potential locus for the development of novel therapeutics focused on induction of the Nrf2-directed antioxidant pathway and inhibition of protein misfolding.
In this study, we found that DDO-7263, a novel Nrf2-ARE activator reported by us, has ideal therapeutic effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice.
Neuroprotective Effects of a Traditional Multi-Herbal Medicine Kyung-Ok-Ko in an Animal Model of Parkinson's Disease: Inhibition of MAPKs and NF-κB Pathways and Activation of Keap1-Nrf2 Pathway.
This study demonstrates that α-SYN and Nrf2 deficiency cooperate on protein aggregation, neuroinflammation and neuronal death and provides a bifactorial animal model to study early-stage PD.
All this makes Nrf2 an optimal target for drugs that could support the mitochondrial quality control, which, in combination with antioxidant protection, can significantly slow down the pathogenesis of PD.
Beneficial effects of n-3 polyunsaturated fatty acids administration in a partial lesion model of Parkinson's disease: The role of glia and NRf2 regulation.
Noncovalent inhibitors of the Keap1-Nrf2 protein-protein interaction (PPI) have therapeutic potential in a range of disease states including neurodegenerative diseases (Parkinson's and Alzheimer's diseases), chronic obstructive pulmonary disease and various inflammatory conditions.
We hypothesized that activation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1, potential therapeutic targets for neurodegeneration) with gintonin could abrogate PD-associated neurotoxicity by modulating the accumulation of α-synuclein, neuroinflammation, and apoptotic cell death in an MPTP/MPP<sup>+</sup> models of PD.
Neuroprotective Effects of Tanshinone I Against 6-OHDA-Induced Oxidative Stress in Cellular and Mouse Model of Parkinson's Disease Through Upregulating Nrf2.
Our data suggest that targeting Nrf2-mediated gene transcription using MMF rather than DMF is a promising approach to block oxidative stress, neuroinflammation, and mitochondrial dysfunction for therapeutic intervention in PD while minimizing side effects.
While CSF Nrf2 and HSPA8 do not appear to offer diagnostic biomarkers for PD, the associations between Nrf2 levels and UPDRS scores in LRRK2 + PD patients merit further investigation.