Activation of Nrf2/ARE pathway alleviates the cognitive deficits in PS1V97L‐Tg mouse model of Alzheimer’s disease through modulation of oxidative stress

Tian, Yaru; Wang, Wei; Xu, Lingzhi; Li, Haitao; Wei, Yiping; Wu, Qiaoqi; Jia, Jianping

doi:10.1002/jnr.24357

Cited by 37 publications

(21 citation statements)

References 56 publications

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“…Eventhough we have proved that high-glucose induced inhibition of HRECs viability, promotion of HRECs apoptosis, inflammation associated cytokines secretion and oxidative stress, the detailed mechanisms and downstream targets of CKIP - 1 are still unknown. Nrf2 / ARE signaling is crucial for the regulation of oxidative stress in multiple diseases, such as neurological disorders [30], Parkinson diseases [31] and Alzheimer’s disease [32]. Of note, Nrf2 / ARE signaling have been reported to be related with DM complications.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Zhang

et al. 2019

Cell Biosci

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Purpose The aim of this study was to investigate the underlying mechanisms of diabetic retinopathy (DR) development. Methods Real-Time qPCR was used to detect Casein kinase 2 interacting protein - 1 ( CKIP - 1 ) and Nuclear factor E2 - related factor 2 ( Nrf2 ) mRNA levels. Western Blot was employed to detect protein levels. Malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) kit and glutathione peroxidase (GSH-Px) kit were used to evaluate oxidative stress in high-glucose treated human retinal endothelial cells (HRECs). Calcein-AM/propidium iodide (PI) double stain kit was employed to detect cell apoptosis. Enzyme-linked ImmunoSorbent Assay (ELISA) was used to detect inflammation associated cytokines secretion. Co-immunoprecipitation (CO-IP) was performed to investigate the interactions between CKIP - 1 and Nrf2 . Luciferase reporter gene system was used to detect the transcriptional activity of Nrf2 . Results CKIP - 1 was significantly downregulated in either DR tissues or high-glucose treated HRECs comparing to the Control groups. Besides, high-glucose (25 mM) inhibited HRECs viability and induced oxidative stress, inflammation associated cytokines (TNF-α, IL-6 and IL-1β) secretion and cell apoptosis, which were all reversed by synergistically overexpressing CKIP - 1 and aggravated by knocking down CKIP - 1 . Of note, we found that overexpressed CKIP - 1 activated Nrf2 / ARE signaling pathway and increased its downstream targets including HO - 1 , NQO - 1 , γGCS and SOD in high-glucose treated HRECs. Further results also showed that CKIP - 1 regulated cell viability, oxidative stress, inflammation and apoptosis in high-glucose treated HRECs by activating Nrf2 / ARE signaling pathway. Conclusion We concluded that overexpressed CKIP - 1 alleviated DR progression by activating Nrf2 / ARE signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Zhang

et al. 2019

Cell Biosci

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“…NrF2 acts on redox homeostasis due to the regulation of target genes involved in the expression of antioxidant enzymes and on the expression of mitochondrial repair factors [96]. A recent study reported the activation of Nrf2 and subsequent binding to antioxidant response elements (ARE), in addition to decreased oxidative stress, β -amyloid (A β ), and improved cognitive function in a mouse model of AD [97]. Therefore, this study suggests possible ways that α -LA could be inducing the overexpression of Nrf2 and promoting improved mitochondrial function in neurons.…”

Section: Molecular Mechanisms Of α-La In Neurodegenerationmentioning

confidence: 99%

Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer’s Disease?

Santos

Romeiro

Rodrigues

et al. 2019

Oxidative Medicine and Cellular Longevity

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Alzheimer's disease (AD) is a neurodegenerative disorder characterised by impairments in the cognitive domains associated with orientation, recording, and memory. This pathology results from an abnormal deposition of the β-amyloid (Aβ) peptide and the intracellular accumulation of neurofibrillary tangles. Mitochondrial dysfunctions play an important role in the pathogenesis of AD, due to disturbances in the bioenergetic properties of cells. To date, the usual therapeutic drugs are limited because of the diversity of cellular routes in AD and the toxic potential of these agents. In this context, alpha-lipoic acid (α-LA) is a well-known fatty acid used as a supplement in several health conditions and diseases, such as periphery neuropathies and neurodegenerative disorders. It is produced in several cell types, eukaryotes, and prokaryotes, showing antioxidant and anti-inflammatory properties. α-LA acts as an enzymatic cofactor able to regulate metabolism, energy production, and mitochondrial biogenesis. In addition, the antioxidant capacity of α-LA is associated with two thiol groups that can be oxidised or reduced, prevent excess free radical formation, and act on improvement of mitochondrial performance. Moreover, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6. Regarding the pharmacokinetic profile, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic. However, α-LA has low risk in prolonged use, although its therapeutic potential, interactions with other substances, and adverse reactions have not been well established in clinical trials with populations at higher risk for diseases of aging. Thus, this review aimed to describe the pharmacokinetic profile, bioavailability, therapeutic efficacy, safety, and effects of combined use with centrally acting drugs, as well as report in vitro and in vivo studies that demonstrate the mitochondrial mechanisms of α-LA involved in AD protection.

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“…Previous study found the mice lacking the Nrf2 transcription had increased oxidative stress in hippocampus, thus resulting in serious cognitive impairment, which was further illustrated by a marked amplification of the oxidative stress and inflammatory response factor (McNeilly et al., 2016). Besides, the activation of Nrf2 would improve the cognitive function of PS1V97L‐Tg mice model of AD (Tian et al., 2019). As reported, compounds activating the Nrf2 pathway, which starts the transcription of antioxidant enzymes, such as BDNF (a growth factor that promotes neuronal survival), have been reported to protect the neurons from a variety of injury (Shi et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

RTA‐408 protects against propofol‐induced cognitive impairment in neonatal mice via the activation of Nrf2 and the inhibition of NF‐κB p65 nuclear translocation

Zhang

Zhou

2020

Brain and Behavior

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Objective To explore the effect of RTA‐408 on the propofol‐induced cognitive impairment of neonatal mice via regulating Nrf2 and NF‐κB p65 nuclear translocation. Methods C57BL/6 neonatal mice were randomized into intralipid, propofol, vehicle + propofol, and RTA‐408 + propofol groups. The learning and memory ability was inspected by Morries water maze (MWM) test. TUNEL staining was performed to examine the apoptosis of neurons in hippocampus. The gene and protein expressions in hippocampus were detected by immunohistochemistry, qRT‐PCR, or Western blotting. The activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were tested by the corresponding kits. Results Propofol prolonged escape latency of mice, decreased the times of crossing the platform, and shortened the time of staying in the target quadrant, while RTA‐408 treatment improved the above‐mentioned situation. Besides, Nrf2 protein in hippocampus of mice induced by propofol was decreased with the increased NF‐κB p65 nuclear translocation, which was reversed by RTA‐408. Meanwhile, RTA‐408 decreased the apoptosis of neurons accompanying with the down‐regulation of Caspase‐3 and the up‐regulations of neuronal‐specific nuclear protein (NeuN), microtubule‐associated protein 2 (Map2), Ca2+/Calmodulin‐dependent Protein Kinase II (CaMKII), and parvalbumin (PV) immunostaining in hippocampus. Besides, propofol‐induced high levels of proinflammatory cytokines and antioxidase activities in hippocampus were reduced by RTA‐408. Conclusion RTA‐408 improved propofol‐induced cognitive impairment in neonatal mice via enhancing survival of neurons, reducing the apoptosis of hippocampal neurons, mitigating the inflammation and oxidative stress, which may be correlated with the activation of Nrf2 and the inhibition of NF‐κB p65 nuclear translocation.

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Activation of Nrf2/ARE pathway alleviates the cognitive deficits in PS1V97L‐Tg mouse model of Alzheimer’s disease through modulation of oxidative stress

Cited by 37 publications

References 56 publications

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer’s Disease?

RTA‐408 protects against propofol‐induced cognitive impairment in neonatal mice via the activation of Nrf2 and the inhibition of NF‐κB p65 nuclear translocation

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