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.
Western blotting results showed that the expression of Nrf2 in the ventral midbrain decreased significantly in the PD mice, and that matrine was able to reverse this phenomenon.
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.
We have previously isolated 2',3'-dihydroxy-4',6'-dimethoxychalcone (DDC) from green perilla leaves as an activator of the nuclear factor erythroid 2-related factor-2 (Nrf2)-antioxidant response element (ARE) and demonstrated the protective effects of DDC both in vitro and in vivo in PC12 cells and Parkinson's disease models, respectively.
We applied an imaging approach to demonstrate the activation of Nrf2 transcription factor as a hallmark of neurodegeneration in neurotoxin-driven models of PD.
We also show that SMF-3 is expressed in DA neurons, Al(3+) exposure results in a significant decrease in protein levels, and the neurodegeneration is partially dependent on the PD-associated transcription factor Nrf2/SKN-1 and caspase Apaf1/CED-4.
Two strategies are known to increase Nrf2 transcriptional activity in PD: i) use of certain catechol-derived quinones for selective inhibition of the Nrf2 repressor Kelch-like ECH-associated protein to increase of Nrf2 protein levels; and ii) use of glycogen synthase kinase 3beta inhibitors to maintain high protein and activity levels of Nrf2 in the nucleus.
Together, this study demonstrates NAR enhanced astroglial neurotrophic effects on DA neurons through the regulation of Nrf2 activation, and these findings might open new potential promising avenues for neurotrophic factor-based treatment of PD.
Thus, activation of the Nrf2 pathway in astrocytes is a potential target to develop therapeutic strategies for treating pathologic synucleinopathies including PD.
This study enrolled a total of 1006 individuals composed of 480 PD patients and 526 controls to evaluate if there was an association of the NFE2L2 promoter polymorphisms with PD susceptibility in the Taiwan population.
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.
This study aimed to investigate the key long non-coding RNAs (lncRNAs) correlated with Nrf2, which might provide valuable information for the exploration of pathogenesis of PD.
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.
These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.
These neuritic defects result from impaired Nrf2 activity on antioxidant response elements (AREs) localized to a microtubule-associated protein (Map1b) gene enhancer and are rescued by forced expression of Map1b as well as by both Nrf2 overexpression and pharmaceutical activation in PD neurons.
The pooled odds ratio (OR) and 95% confidence interval were calculated to assess the genetic association between the NFE2L2rs35652124 polymorphism and the risk of PD.
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.
The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which is a cellular defense system against oxidative stress, is a promising target for therapeutics aimed at reducing neuronal death in PD.
Taken together, our results strongly suggest that Tan IIA may be beneficial for the treatment of PD, and also confirm that targeting the Nrf2/ARE pathway is a promising strategy for therapeutic intervention in PD.
Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD).