Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders

Dwivedi, Divya; Megha, Kanu; Mishra, Ritwick; Mandal, Pravat K.

doi:10.1007/s11064-020-03030-1

Cited by 98 publications

(62 citation statements)

References 197 publications

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“…The change in their oxidized/reduced form ratio occurs as a reaction to changes in reactive oxygen and nitrogen species (RONS) levels and, so, they can play the role of a trigger in the redox-dependent regulation of cellular processes. Undoubtedly, such an important trigger role is played by glutathione (γ-glutamyl-L-cysteinylglycine, GSH), a water-soluble tripeptide consisting of the amino acids L-glutamate, L-cysteine, and glycine, which is widely present in both eukaryotes and prokaryotes [1][2][3]. GSH is less susceptible to oxidation than Cys, which makes it the most suitable for maintaining intracellular redox status [1].…”

Section: Introductionmentioning

confidence: 99%

“…Undoubtedly, such an important trigger role is played by glutathione (γ-glutamyl-L-cysteinylglycine, GSH), a water-soluble tripeptide consisting of the amino acids L-glutamate, L-cysteine, and glycine, which is widely present in both eukaryotes and prokaryotes [1][2][3]. GSH is less susceptible to oxidation than Cys, which makes it the most suitable for maintaining intracellular redox status [1]. The presence of a γ-peptide bond at the Glu residue protects GSH from the action of peptidases, while the SH group at the Cys residue makes GSH a good electron donor, allowing it to participate in reactions with strong electrophiles.…”

Section: Introductionmentioning

confidence: 99%

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Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation

Калинина

Novichkova

2021

Molecules

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S-glutathionylation and S-nitrosylation are reversible post-translational modifications on the cysteine thiol groups of proteins, which occur in cells under physiological conditions and oxidative/nitrosative stress both spontaneously and enzymatically. They are important for the regulation of the functional activity of proteins and intracellular processes. Connecting link and “switch” functions between S-glutathionylation and S-nitrosylation may be performed by GSNO, the generation of which depends on the GSH content, the GSH/GSSG ratio, and the cellular redox state. An important role in the regulation of these processes is played by Trx family enzymes (Trx, Grx, PDI), the activity of which is determined by the cellular redox status and depends on the GSH/GSSG ratio. In this review, we analyze data concerning the role of GSH/GSSG in the modulation of S-glutathionylation and S-nitrosylation and their relationship for the maintenance of cell viability.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation

Калинина

Novichkova

2021

Molecules

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“…GSH has been measured by 1 H-MRS in humans in a number of neurological diseases such as Alzheimer's disease ( 30 ), schizophrenia ( 31 ), and epilepsy ( 32 ). To our knowledge, this study was the first to investigate the changes in brain GSH in migraineurs using 1 H-MRS. GSH is the major cellular antioxidant that is essential for cellular function, plays roles in oxidation–reduction reactions, and protects against reactive oxygen species ( 33 , 34 ). Our study found decreased GSH/tCr levels in the occipital lobe of MWoA-DA patients suggesting enhanced oxidative stress and a depletion of antioxidant defenses during the migraine attack; thus, the decreased GSH/tCr levels is the result, rather than the cause, of migraine attacks, as there was no difference between MWoA-DI and HC.…”

Section: Discussionmentioning

confidence: 99%

Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period

et al. 2021

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Background: Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.Methods: Six patients (one man and five women, mean age: 39 ± 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 ± 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 ± 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.Results: The MWoA-DA patients had lower glutathione/total creatine ratio (GSH/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline/total creatine ratio (tCho/tCr) than those in the other two groups. The GSH/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.Conclusion: The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.

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“…Moreover, the oxidative damage on DNA results in the formation of oxidized base adduct including 8-hydroxyguanine (8-OHG), 8-hydroxyadenine (8-OHA), and 5,6-diamino-5-formamidopyrimidine in both nuclear and mitochondrial DNA of the brain of patients with mild cognitive impairment (MCI), the earliest clinical manifestation of AD [ 56 ]. Despite the high capacity of ROS generation in the brain, the organ’s defense mechanism against oxidative stress remains limited and reduced in ageing, due to low concentrations of endogenous antioxidants including CAT, GSH, GPX, and vitamin E compared to the liver [ 57 , 58 , 59 , 60 , 61 , 62 ]. The restricted regenerative capacity of postmitotic neuron cells has made oxidative stress more destructive to the brain, in which the lesion is permanent and accumulates over time compared to other organs [ 63 , 64 ].…”

Section: Free Radicals and Oxidative Damage To Biomoleculesmentioning

confidence: 99%

A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases

et al. 2020

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Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption.

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Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders

Cited by 98 publications

References 197 publications

Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation

Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation

Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period

A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases

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