The impact of glutathione metabolism in autism spectrum disorder

Bjørklund, Geir; Doşa, Monica Daniela; Maes, Michaël; Dadar, Maryam; Frye, Richard E.; Peana, Massimiliano; Chirumbolo, Salvatore

doi:10.1016/j.phrs.2021.105437

Cited by 33 publications

(27 citation statements)

References 210 publications

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Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

“…Neuroinflammation is closely related to OS and associated with neurodevelopmental disorders [101][102][103][104]. Supraphysiological intracellular levels of ROS induce the production of proinflammatory cytokines from astrocytes and microglia [101,104]. These cytokines activate NOX of astrocytes and microglia, resulting in a vicious cycle of OS and neuroinflammation [103,105].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

“…These cytokines activate NOX of astrocytes and microglia, resulting in a vicious cycle of OS and neuroinflammation [103,105]. The neuroinflammation may lead to neuronal apoptosis and alterations of homeostatic levels of neurotransmitters [102,104]. Neuroinflammation can be assessed in rodents [106], zebrafish [107], and pluripotent stem cells [108].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

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Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

Nishimura

Kanda

Sone

et al. 2021

Oxidative Medicine and Cellular Longevity

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The developing brain is extremely sensitive to many chemicals. Perinatal exposure to neurotoxicants has been implicated in several neurodevelopmental disorders, including autism spectrum disorder, attention-deficit hyperactive disorder, and schizophrenia. Studies of the molecular and cellular events related to developmental neurotoxicity have identified a number of “adverse outcome pathways,” many of which share oxidative stress as a key event. Oxidative stress occurs when the balance between the production of free oxygen radicals and the activity of the cellular antioxidant system is dysregulated. In this review, we describe some of the developmental neurotoxins that target the antioxidant system and the mechanisms by which they elicit stress, including oxidative phosphorylation in mitochondria and plasma membrane redox system in rodent models. We also discuss future directions for identifying adverse outcome pathways related to oxidative stress and developmental neurotoxicity, with the goal of improving our ability to quickly and accurately screen chemicals for their potential developmental neurotoxicity.

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Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

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Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

Nishimura

Kanda

Sone

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Glutathione can regulate glutamate receptors including the N- methyl-D-aspartate (NMDA) receptor, which can contribute to glutamate excitotoxicity. Interactions between glutamate and glutathione can result in neuronal dysfunction and involve the NF-κB pathway [ 114 ]. Treatment with NAC was shown to have clinical improvement in critically ill COVID-19 patients [ 115 ].…”

Section: Potential Therapeutics Of Nf-κb Modulators In Covid‑19 Infectionmentioning

confidence: 99%

The Effect of COVID-19 on NF-κB and Neurological Manifestations of Disease

2021

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The coronavirus disease that presumably began in 2019 (COVID-19) is a highly infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic. Initially, COVID-19 was thought to only affect respiration. However, accumulating evidence shows a wide range of neurological symptoms are also associated with COVID-19, such as anosmia/ageusia, headaches, seizures, demyelination, mental confusion, delirium, and coma. Neurological symptoms in COVID-19 patients may arise due to a cytokine storm and a heighten state of inflammation. The nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) is a central pathway involved with inflammation and is shown to be elevated in a dose-dependent matter in response to coronaviruses. NF-κB has a role in cytokine storm syndrome, which is associated with greater severity in COVID-19-related symptoms. Therefore, therapeutics that reduce the NF-κB pathway should be considered in the treatment of COVID-19. Neuro-COVID-19 units have been established across the world to examine the neurological symptoms associated with COVID-19. Neuro-COVID-19 is increasingly becoming an accepted term among scientists and clinicians, and interdisciplinary teams should be created to implement strategies for treating the wide range of neurological symptoms observed in COVID-19 patients.

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“…The glutathione system is an important player in maintaining redox balance in intracellular redox pathways, particularly in the brain, explaining why decreased GSH defenses with increased ROS can have disastrous consequences, including oxidative CNS damage (Bermejo et al, 2008;Pocernich and Butterfield, 2012). Furthermore, GSH is required for xenobiotic detoxification, and low GSH levels are linked to neuronal apoptosis and mitochondrial dysfunction, whereas GSHdependent N-methyl-D-aspartate receptor modulation regulates glutamate excitotoxicity (Bjørklund et al, 2021;Morris et al, 2014). Furthermore, decreased GSH defenses and GSH oxidation are linked to dysfunctions in macrophage functions, dendritic cell maturation and differentiation, antigen presentation, neutrophil respiratory burst and extracellular trap production, and T cell regulatory functions (Morris and Maes, 2021) .…”

Section: Antioxidant Levels In MCImentioning

confidence: 99%

Oxidative stress and antioxidant defenses in mild cognitive impairment: a systematic review and meta-analysis

Nantachai

Maes

Tunvirachaisakul

et al. 2021

Preprint

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This study aims to systematically review and meta-analyze the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of people with mild cognitive impairment (MCI). We searched PubMed, Scopus, Google Scholar, and Web of Science for articles published from inception until July 31, 2021. Forty-six studies on 3.798 MCI individuals and 6.063 healthy controls were included. The O&NS/ANTIOX ratio was significantly higher in MCI than in controls with a Standardized Mean Difference (SMD)=0.378 (95% CI: 0.250; 0.506). MCI individuals showed increased lipid peroxidation (SMD=0.774, 95%CI: 4.416; 1.132) and O&NS-associated toxicity (SMD=0.621, CI: 0.377; 0.865) and reduced glutathione (GSH) defenses (SMD=0.725, 95%CI: 0.269; 1.182) as compared with controls. MCI was also accompanied by significantly increased homocysteine (SMD=0.320, CI: 0.059; 0.581), but not protein oxidation, and lowered non-vitamin (SMD=0.347, CI: 0.168; 0.527) and vitamin (SMD=0.564, CI: 0.129; 0.999) antioxidant defenses. The results show that MCI is at least in part due to increased neuro-oxidative toxicity and suggest that treatments targeting lipid peroxidation and the GSH system may be used to treat or prevent MCI.

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The impact of glutathione metabolism in autism spectrum disorder

Cited by 33 publications

References 210 publications

Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

The Effect of COVID-19 on NF-κB and Neurological Manifestations of Disease

Oxidative stress and antioxidant defenses in mild cognitive impairment: a systematic review and meta-analysis

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