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.
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.
This article describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including sirtuin and Nrf2 and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases.
Given the attention Nrf2 is receiving as a potential therapeutic target in AxD and other neurodegenerative diseases, it will be interesting to see whether induction of Nrf2, beyond the endogenous response, is beneficial or not in these same models.
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.
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.
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.
In this review, we summarize the progress of the Nrf2-ARE pathway in combating toxicity induced from typical misfolded protein aggregates in neurodegenerative diseases, and specifically the effects on the clearance of protein aggregates.
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.
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.
This study identifies ASK1/JNK and ASK1/p38 as two critical pathways involved in the activation of cell death under oxidative stress conditions and identifies the Nrf2/Trx axis as a new target to block these pathways and protect from oxidant exposure such as that found in Parkinson and other neurodegenerative diseases.
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).