Critical Roles of Glutaredoxin in Brain Cells—Implications for Parkinson's Disease

Miller, Olga Gorelenkova; Mieyal, John J.

doi:10.1089/ars.2017.7411

Cited by 21 publications

(15 citation statements)

References 134 publications

(163 reference statements)

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“…Furthermore, analyses of qRT-PCR, Western blotting, ELISA, CCK-8 assay and flow cytometry elaborated that miR-132-3p interfered with microglial activation and neuronal injury by targeting GLRX. Our data are in agreement with the earlier findings showing that enhancement of GLRX activity in these brain cells would impede the progression of PD ( Gorelenkova Miller and Mieyal, 2019 ). MPTP is a neurotoxin that results in a profound reduction of striatal dopamine levels and specific loss of dopaminergic neurons in animals ( Lee et al, 2019 ).…”

Section: Discussionsupporting

confidence: 94%

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Gong

Huang

Chen

2022

eNeuro

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The major pathology in Parkinson's disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation of microglial cells. The objective of this study is to determine the effect and mechanism of miR-132-3p in regulating neuroinflammation and the degeneration of dopaminergic neuron in PD.The expressions of miR-132-3p in brain tissues of PD patients, LPS induced BV-2 cells and MPTP induced PD mouse models were detected. The effect of miR-132-3p and GLRX in cell viability, apoptosis and inflammation was verified in BV-2 cells.The activation of Iba1 in substantia nigra pars compacta and the loss of tyrosine hydroxylase were detected in PD mouse models and the mobility of mouse models was assessed as well. The targeting relationship between miR-132-3p and GLRX was confirmed by RIP and dual luciferase reporter gene assay. Elevated expression of miR-132-3p and decreased expression of GLRX were found in PD patients and cells models. Overexpression of miR-132-3p can induce activation of microglial cells, which can be reversed by GLRX overexpression. Collected evidence in both cell model and mouse models showed the effect of miR-132-3p in enhancing the activation of microglial cells and the loss of microglia cells, which was achieved by mediating GLRX.

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Section: Discussionsupporting

confidence: 94%

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Gong

Huang

Chen

2022

eNeuro

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“…Grx is an essential thioltransferase whose primary role is to reduces S-glutathionylation. Grx 1 insufficiency results in increased levels of S-glutathionylation, implicated in many pathological events, including cardiovascular [56] and Parkinson's [57] diseases. Since Grx catalyzes GSH-dependent reduction of S-glutathionylation, lower GSH:GSSG ratio might attenuate Grx activity, mimicking Grx deficiency.…”

Section: The Biological Meaning Of Protein S-glutathionylationmentioning

confidence: 99%

“…Since Grx catalyzes GSH-dependent reduction of S-glutathionylation, lower GSH:GSSG ratio might attenuate Grx activity, mimicking Grx deficiency. In contrast, Grx 1 plays a primary proinflammatory role in microglia [57] or an anti-angiogenic role in the vasculature [58]. More than one hundred S-glutathionylation proteins have been experimentally verified.…”

Section: The Biological Meaning Of Protein S-glutathionylationmentioning

confidence: 99%

Oxidative Stress Orchestrates MAPK and Nitric-Oxide Synthase Signal

Takata

Araki

Tsuchiya

et al. 2020

IJMS

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Reactive oxygen species (ROS) are not only harmful to cell survival but also essential to cell signaling through cysteine-based redox switches. In fact, ROS triggers the potential activation of mitogen-activated protein kinases (MAPKs). The 90 kDa ribosomal S6 kinase 1 (RSK1), one of the downstream mediators of the MAPK pathway, is implicated in various cellular processes through phosphorylating different substrates. As such, RSK1 associates with and phosphorylates neuronal nitric oxide (NO) synthase (nNOS) at Ser847, leading to a decrease in NO generation. In addition, the RSK1 activity is sensitive to inhibition by reversible cysteine-based redox modification of its Cys223 during oxidative stress. Aside from oxidative stress, nitrosative stress also contributes to cysteine-based redox modification. Thus, the protein kinases such as Ca2+/calmodulin (CaM)-dependent protein kinase I (CaMKI) and II (CaMKII) that phosphorylate nNOS could be potentially regulated by cysteine-based redox modification. In this review, we focus on the role of post-translational modifications in regulating nNOS and nNOS-phosphorylating protein kinases and communication among themselves.

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“…Recent studies showed that overexpression of Grx1 inhibited monocyte chemotaxis induced by MCP-1 (48), and Grx1 KO mice are more susceptible to pulmonary fibrosis (49). Elevated Grx1 activity diminishes the development of Parkinson's disease (50). However, few studies have reported interactions of Grx1 and VLA4 in those processes, which need further investigation.…”

Section: Regulation Of ␣4 Integrin By Glutathionylationmentioning

confidence: 99%

Glutaredoxin 1 up-regulates deglutathionylation of α4 integrin and thereby restricts neutrophil mobilization from bone marrow

You

Chen

Zhu

et al. 2019

Journal of Biological Chemistry

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Figure 7. Schematic of Grx1 and ROS involvement in neutrophil mobilization from the bone marrow via integrin ␣4/VCAM-1. Under stress conditions, the level of ROS is elevated in the bone marrow microenvironment. ROS induced the glutathionylation of ␣4 integrin in neutrophils, which increased the affinity of ␣4 of neutrophils to VCAM-1 on endothelial cells in the bone marrow. Furthermore, glutathionylation of ␣4 promoted neutrophil mobilization from the bone marrow. These effects were negatively mediated by Grx1. Regulation of ␣4 integrin by glutathionylation

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Critical Roles of Glutaredoxin in Brain Cells—Implications for Parkinson's Disease

Abstract: Further investigation is needed to understand the preponderant role of Grx1 regarding dopaminergic neuronal survival. Antioxid. Redox Signal. 00, 000-000.

Cited by 21 publications

References 134 publications

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Oxidative Stress Orchestrates MAPK and Nitric-Oxide Synthase Signal

Glutaredoxin 1 up-regulates deglutathionylation of α4 integrin and thereby restricts neutrophil mobilization from bone marrow

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