In this review, we outline the role that oxidative stress and the reduction of NRF2 play in each of the Hallmarks of Aging, including how they contribute to the onset of neurodegenerative disorders, cancer, and other age-related pathologies.
Interestingly, sulforaphane-enriched broccoli sprouts improved the scopolamine-induced memory impairment in mice through Nrf2 activation, inhibiting neuronal apoptosis particularly through inhibition of caspase-3 activation which could lead to the neuroprotection against neurodegenerative disorders.
The damaged function and altered localization of NRF2 are found in most neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis.
Overall, eriodictyol protects LPS-triggered oxidative stress, neuroinflammation, and synaptic dysfunctions partially through MAPKs, NF-κB mediated by ROS, Sirt1, and Nrf2/Keap1 signal pathways, which further supports that eriodictyol is a potentially nutritional preventive strategy for oxidative stress-related neurodegenerative diseases.
Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether β-LAP induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains.
Activation of Nrf2/ARE signaling can mitigate several pathologic mechanisms associated with an autoimmune response, digestive and metabolic disorders, as well as respiratory, cardiovascular, and neurodegenerative diseases.
Therefore, the nuclear factor-E2-related factor 2 (Nrf2), a key regulator of the antioxidative response, is considered to be important as a therapeutic target for neurodegenerative diseases.
Although plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) protects against cerebral ischemia and spinal cord injury-induced oxidative stress and inflammation by activating the nuclear factor-erythroid 2-related factor-2 /antioxidant response element (Nrf2/ARE) pathway, its role in the amelioration of neurodegenerative diseases remains unexplored.
SIRT1 and NRF2 stimulate anti-inflammatory mechanisms and have previously demonstrated therapeutic value in preclinical models of neurodegenerative disease.
Small molecule pharmacological activators of Nrf2 have shown protective effects in numerous animal models of neurodegenerative diseases, and in cultures of human cells expressing mutant proteins.
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.
Our results showed important multi-protective effects of DMF pre-treatment from Aβ stimulation both in in vitro and ex vivo models, highlighting an Nrf2/NF-κB-dependent mechanism, which could provide a valuable support to the therapies for neurodegenerative diseases today.
Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's and Parkinson's diseases.
The results indicated that FPP enhances the anti-oxidative capacity through activation of Nrf2 in astrocytes, suggesting it may provide neuroprotection in oxidative stress-related neurodegenerative diseases.
Together, this research substantiated a new mechanism that TSG protectively antagonized Aβ-induced hippocampal neuronal cell damage by restoring mitochondrial function via Nrf2-HO-1 pathway, implying a promising candidate against neurodegenerative diseases including AD.
A case in point is redox homeostasis, maintained by antioxidant defences co-ordinately regulated by the transcription factor Nrf2, and capable of preventing not only oxidative stress but also inflammation and neuronal loss in neurodegenerative disease models.
These findings suggested that pretreatment with tBHQ protected PC12 cells from FS-induced oxidative and inflammatory injury via the Nrf2/ARE pathway. tBHQ was promising as a potential therapeutic agent for neurodegenerative diseases induced by iron toxicity and should be encouraged for further research.
Our results demonstrate that CD is a novel small molecule activator of Nrf2 in PC12 cells, and suggest that CD may be a potential candidate for the prevention of oxidative stress-mediated neurodegenerative disorders.
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD).