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… 
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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.
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.
...
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