Glutathione redox imbalance in brain disorders

@article{Gu2015GlutathioneRI,
  title={Glutathione redox imbalance in brain disorders},
  author={Feng Gu and Ved Chauhan and Abha Chauhan},
  journal={Current Opinion in Clinical Nutrition and Metabolic Care},
  year={2015},
  volume={18},
  pages={89–95}
}
  • F. Gu, V. Chauhan, A. Chauhan
  • Published 1 January 2015
  • Biology, Medicine, Psychology
  • Current Opinion in Clinical Nutrition and Metabolic Care
Purpose of reviewGlutathione (GSH) is a major endogenous antioxidant. Several studies have implicated GSH redox imbalance in brain disorders. Here, we summarize current evidence on how GSH depletion and GSH-related enzyme deficit are involved in the pathology of brain disorders such as autism, schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease. Recent findingsMany studies with animal models of various brain disorders and/or with clinical samples from humans with… 
View on Wolters Kluwer
ncbi.nlm.nih.gov
158 Citations
Highly Influential Citations
6
Background Citations
54
Methods Citations
1

158 Citations

The impact of glutathione metabolism in autism spectrum disorder.
The role of glutathione redox imbalance in autism spectrum disorder: A review.
Glutathione in Brain Disorders and Aging
TLDR
This review will highlight the common signaling cascades that regulate glutathione in neurons and glia, its functions as a neuronal regulator in homeostasis and metabolism, and finally a mechanistic recapitulation ofglutathione signaling, which will put glutathion’s role in normal aging and neurological disorders development into perspective.
In Vivo Brain GSH: MRS Methods and Clinical Applications
TLDR
The definition of standard reference values for different brain areas could lead to a better interpretation of the altered GSH levels recorded in subjects with neurological disorders, with insights into the possible role of GSH as a biomarker and therapeutic target.
The glutathione system in Parkinson’s disease and its progression
Altered central and blood glutathione in Alzheimer’s disease and mild cognitive impairment: a meta-analysis
TLDR
Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD, and potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.
Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement
TLDR
Evidence for redox imbalance in the brain in all phases of SZ, potentially reflecting oxidative stress is provided by a significant reduction in the NAD+/NADH ratio in chronically ill SZ patients compared to a matched healthy control group, and in FE SZ customers compared to both a matched FE BD patient group and a matchedhealthy control group.
N-Acetylcysteine Mitigates Social Dysfunction in a Rat Model of Autism Normalizing Glutathione Imbalance and the Altered Expression of Genes Related to Synaptic Function in Specific Brain Areas
TLDR
The effects of repeated NAC administration on core autistic-like features and altered brain GSH metabolism in the VPA rat model of ASD indicate that NAC treatment selectively mitigates the social dysfunction displayed by VPA-exposed rats normalizing GSH imbalance and reestablishing the expression of genes related to synaptic function in a brain region-specific manner.
Do glutathione and copper interact to modify Alzheimer's disease pathogenesis?
Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide
TLDR
Early effects of iAs exposure on glutathione levels were not homogeneous among different brain regions and indicate early neurotoxic alterations in the cortex and cerebellum.
...
...

References

SHOWING 1-10 OF 62 REFERENCES
Brain Region-Specific Glutathione Redox Imbalance in Autism
TLDR
It is suggested that disturbances in brain glutathione homeostasis may contribute to oxidative stress, immune dysfunction and apoptosis, particularly in the cerebellum and temporal lobe, and may lead to neurodevelopmental abnormalities in autism.
Impaired Glutathione Synthesis in Neurodegeneration
TLDR
Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain.
Redox dysregulation in the pathophysiology of schizophrenia and bipolar disorder: insights from animal models.
TLDR
Experimental data from rodent models demonstrate the usefulness of GSH-deficient rodent models to identify the mechanisms by which a redox imbalance could contribute to the development of SZ and BD pathophysiologies, and to develop novel therapeutic approaches based on antioxidant and redox regulator compounds.
Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases
TLDR
The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutATHione as a biomarker, are critically evaluated.
Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems
TLDR
The beneficial properties of medicinal-chemistry- and technology-based approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases, are discussed.
Glutathione-related factors and oxidative stress in autism, a review.
TLDR
The role of oxidative stress, plasma glutathione (GSH), and related factors as the potential sources of damage to the brain as well as the possible related factors which reduce the oxidative stress are reviewed.
Impaired synthesis and antioxidant defense of glutathione in the cerebellum of autistic subjects: alterations in the activities and protein expression of glutathione-related enzymes.
The emerging role of glutathione in Alzheimer's disease.
TLDR
The present manuscript integrates findings from various studies to elucidate the possible molecular mechanisms through which disruptions in GSH homeostasis may contribute to AD pathology.
Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain
TLDR
Results indicate that decreased GSH/GSSG redox/antioxidant capacity and increased oxidative stress in the autism brain may have functional consequence in terms of a chronic inflammatory response, increased mitochondrial superoxide production, and oxidative protein and DNA damage.
N-acetylcysteine Boosts Brain and Blood Glutathione in Gaucher and Parkinson Diseases
TLDR
This work shows the potential utility of MRS monitoring, which could assist in determining dosing regimens for clinical trials of this potentially useful antioxidant therapy for PD disease, GD, and other neurodegenerative disorders.
...
...