Increasing glutathione levels by a novel posttranslational mechanism inhibits neuronal hyperexcitability

Sri Hari, Ashwini; Banerji, Rajeswari; Liang, Li-Ping; Fulton, Ruth E.; Huynh, Christopher Quoc; Fabisiak, Timothy; McElroy, Pallavi Bhuyan; Roede, James R.; Patel, Manisha

doi:10.1016/j.redox.2023.102895

Cited by 4 publications

(1 citation statement)

References 197 publications

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“…Increased posttranslational modification of the biosynthetic enzyme glutamate cysteine ligase increases intracellular GSH levels, which in turn decreases neuronal hyperexcitability in primary cerebrocortical neuronal-glial cultures; this is the mechanism by which the dithiol-containing compound dimercaprol can increase the intracellular GSH concentration. Treating Dravet syndrome model zebrafish larvae with dimercaprol increases their GSH levels and preventes convulsive, abrupt "seizurelike" swimming behaviour [78].…”

Section: Imbalance Of the Gpx4/gsh Redox Pathway In Epilepsymentioning

confidence: 99%

Insight into the Role of Ferroptosis in Epilepsy

Huang,

Liu,

Liu

2024

J. Integr. Neurosci.

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Excessively high or synchronized neuronal activity in the brain is the underlying cause of epilepsy, a condition of the central nervous system. Epilepsy is caused mostly by an imbalance in the activity of inhibitory and excitatory neural networks. Recurrent or prolonged seizures lead to neuronal death, which in turn promotes epileptogenesis and epileptic seizures. Ferrous ion-mediated cell death is known as ferroptosis, which is due to the accumulation of lipid peroxidation products resulting from compromise of the glutathione (GSH)-dependent antioxidant system. The pathophysiology of epilepsy has been linked to anomalies in the glutathione peroxidase 4 (GPX4)/GSH redox pathway, lipid peroxidation, and iron metabolism. Studies have shown that inhibiting ferroptosis may alleviate cognitive impairment and decrease seizures, indicating that it is neuroprotective. With the hope of aiding the development of more novel approaches for the management of epilepsy, this research aimed to examine the role of ferroptosis in this disease.

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Section: Imbalance Of the Gpx4/gsh Redox Pathway In Epilepsymentioning

confidence: 99%

Insight into the Role of Ferroptosis in Epilepsy

Huang,

Liu,

Liu

2024

J. Integr. Neurosci.

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Pharmacological elevation of glutathione inhibits status epilepticus-induced neuroinflammation and oxidative injury

Liang,

Sri Hari,

Day

et al. 2024

Redox Biology

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Identification of a novel TSC1 variant in a family with developmental and epileptic encephalopathies: A case report and literature review

Wang,

Zhai,

Chen

2024

Medicine

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Rationale: Tuberous sclerosis (TSC) is an autosomal dominant neurocutaneous syndrome resulting from mutations in the tumor suppressor genes TSC1 and TSC2. Unfortunately, the absence of accurate diagnosis has significantly impacted the well-being of both patients and their families. Furthermore, the pathogenicity of numerous variants remains unverified, which could potentially result in misinterpretation of their functional implications. Patient concerns: Proband 1 was a 33-year-old Chinese male, this patient presents with hamartomas in multiple organ systems, accompanied by clinical symptoms such as intellectual disability, epilepsy, and lipid adenoma. The patient and their family members used targeted next-generation sequencing and Sanger sequencing to identify the pathogenic variant. Diagnoses: The TSC1 (c.2923G>T, c.2924C>T) variant was identified and the patient was diagnosed with TSC disease. Interventions: After the definite diagnosis, the patient was treated with valproic acid, oxcarbazepine, and various organ supports. Outcomes: At present, the patient has intellectual decline, multiple sebaceous adenomas, multiple fiber nodules on the back, palpable mass in the right subcostal and middle upper abdomen, and percussion pain in the right kidney area, 1 to 2 times a month seizure, poor intelligence than peers. Lessons: This finding strengthens the significant phenotypic variability associated with TSC and expands the mutational spectrum of this rare disease.

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Increasing glutathione levels by a novel posttranslational mechanism inhibits neuronal hyperexcitability

Cited by 4 publications

References 197 publications

Insight into the Role of Ferroptosis in Epilepsy

Insight into the Role of Ferroptosis in Epilepsy

Pharmacological elevation of glutathione inhibits status epilepticus-induced neuroinflammation and oxidative injury

Identification of a novel TSC1 variant in a family with developmental and epileptic encephalopathies: A case report and literature review

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