Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) and Mitochondrial Dynamics/Mitophagy in Neurological Diseases

Kang, Tae‐Cheon

doi:10.3390/antiox9070617

Cited by 75 publications

(51 citation statements)

References 117 publications

(269 reference statements)

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“…In contrast to mitochondrial fission (Zhou et al, 2018b;Wang et al, 2020c), fusion is associated with a drop in the number of mitochondria but an increase in the quality of mitochondria. It must take place before damaged mitochondria can be repaired by a healthy mitochondrion (Kang, 2020;Wang et al, 2020,d). Fusion is also necessary for the exchange of metabolic substrates between two mitochondria.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Liu

Huang

2020

Front. Cell Dev. Biol.

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Mitochondria are potential targets for the treatment of cardio-cerebrovascular ischemiareperfusion (I/R) injury. However, the role of the mitofusin 2 (Mfn2) protein in regulating mitochondrial fusion and cell survival has not been investigated. In the present study, an adenovirus-mediated Mfn2 overexpression assay was performed to understand the effects of Mfn2 on mitochondrial function and cell damage during cardiocerebrovascular I/R injury. After exposure to I/R injury in vitro, the transcription and expression of Mfn2 were significantly downregulated, which correlated with decreased cell viability and increased apoptosis. By contrast, overexpression of Mfn2 significantly repressed I/R-mediated cell death through modulation of glucose metabolism and oxidative stress. Furthermore, Mfn2 overexpression improved mitochondrial fusion in cells, an effect that was followed by increased mitochondrial membrane potential, improved mitophagy, and inhibition of mitochondria-mediated apoptosis. Our data also demonstrated that Mfn2 overexpression was associated with activation of the AMPK/Sirt3 signaling pathway. Inhibition of the AMPK/Sirt3 pathway abolished the protective effects of Mfn2 on I/R-induced cell injury arising from mitochondrial damage. Our results indicate that Mfn2 protects against cardio-cerebrovascular I/R injury by augmenting mitochondrial fusion and activating the AMPK/Sirt3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Liu

Huang

2020

Front. Cell Dev. Biol.

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“…Mitochondria are known as one of the primary sources of cellular ROS production. Nrf2 signaling is observed to counteract the mitochondria-derived ROS [ 44 ]. Its mechanism is summarized as the following three aspects.…”

Section: Discussionmentioning

confidence: 99%

Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice

Luo

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress and neuronal apoptosis play crucial roles in secondary brain injury (SBI) after intracerebral hemorrhage (ICH). Recently, Nle4-D-Phe7-α-melanocyte-stimulating hormone (NDP-MSH), a synthetic agonist of the melanocortin-1 receptor (Mc1r), has been proved to inhibit neuroinflammatory in several diseases. This study is aimed at exploring if NDP-MSH could reduce oxidative stress and neuronal apoptosis following ICH, as well as the potential mechanism. A mouse ICH model was induced by autologous blood injection. NDP-MSH was intraperitoneally injected at 1 h after ICH. Mc1r siRNA and PI3K inhibitor LY294002 were administrated to inhibit the expression of Mc1r and phosphorylation of PI3K, respectively. Neurological test, brain water content, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunofluorescence, and Western blot analysis were utilized in this study. The results exhibited that Mc1r was mainly expressed in neurons, and its level in the ipsilateral hemisphere was significantly elevated after ICH. NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis. The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3. Conversely, downregulating the expression of Mc1r and phosphorylation of PI3K aggravated the neurological deficits and brain edema at 24 hours after ICH, meanwhile, the effect of NDP-MSH on the expression of Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2, and cleaved caspase 3 was also abolished. In conclusion, our data suggest that the activation of Mc1r by NDP-MSH ameliorates oxidative stress and neuronal apoptosis through the PI3K/Akt/Nrf2 signaling pathway after ICH in mice.

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“…Nrf2 is known to be a redox-sensitive transcription factor which induces antioxidant and detoxifying enzymes in order to protect cells from oxidative stress [ 81 ]. It has shown that Nrf2 activation is able to suppress mitochondrial oxidative stress and is beneficial for suppressing disease pathology including epilepsy [ 16 ].…”

Section: Mitochondrially Targeted Antioxidants As Neuroprotective mentioning

confidence: 99%

Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy

Yang

Guan

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

108

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Mitochondria are major sources of reactive oxygen species (ROS) within the cell and are especially vulnerable to oxidative stress. Oxidative damage to mitochondria results in disrupted mitochondrial function and cell death signaling, finally triggering diverse pathologies such as epilepsy, a common neurological disease characterized with aberrant electrical brain activity. Antioxidants are considered as promising neuroprotective strategies for epileptic condition via combating the deleterious effects of excessive ROS production in mitochondria. In this review, we provide a brief discussion of the role of mitochondrial oxidative stress in the pathophysiology of epilepsy and evidences that support neuroprotective roles of antioxidants targeting mitochondrial oxidative stress including mitochondria-targeted antioxidants, polyphenols, vitamins, thiols, and nuclear factor E2-related factor 2 (Nrf2) activators in epilepsy. We point out these antioxidative compounds as effectively protective approaches for improving prognosis. In addition, we specially propose that these antioxidants exert neuroprotection against epileptic impairment possibly by modulating cell death interactions, notably autophagy-apoptosis, and autophagy-ferroptosis crosstalk.

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Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) and Mitochondrial Dynamics/Mitophagy in Neurological Diseases

Cited by 75 publications

References 117 publications

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice

Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy

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