The glutathione cycle shapes synaptic glutamate activity

Sedlak, Thomas W.; Paul, Bindu D.; Parker, Gregory M.; Hester, Lynda D.; Snowman, Adele M.; Taniguchi, Yu; Kamiya, Atsushi; Snyder, Solomon H.; Sawa, Akira

doi:10.1073/pnas.1817885116

Cited by 147

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The glutathione cycle shapes synaptic glutamate activity

Sedlak, Thomas W., Paul, Bindu D., Parker, Gregory M., Hester, Lynda D., Snowman, Adele M., Taniguchi, Yu, Kamiya, Atsushi, Snyder, Solomon H., Sawa, Akira·2019·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1817885116

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Abstract

Significance: Glutathione is a major antioxidant and redox regulator in cells. In addition to its essential roles in redox homeostasis, it functions as cofactors for a multitude of enzymes. We show here that the glutathione cycle molds the activity of synaptic glutamate, the major excitatory neurotransmitter in the central nervous system. Deficits in glutathione have been linked to multiple neurodegenerative and neuropsychiatric disorders. Accordingly, agents that restore glutathione-glutamate homeostasis may afford therapeutic benefit.

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Glutamate plays roles in cells including imparting antioxidant effects via synthesis of reduced glutathione (GSH).
“In addition to its role as an excitatory neurotransmitter, glutamate also plays other important roles in cells including imparting antioxidant effects via the synthesis of reduced glutathione (GSH) [118].”
From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [118]

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Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling
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Authors: Sedlak, T. W., Paul, B. D., Parker, G. M., Hester, L. D., Snowman, A. M., Taniguchi, Y., Kamiya, A., Snyder, S. H., & Sawa, A.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2019-01-28
Volume: 116
Issue: 7
Pages: 2701-2706
ISSN: 0027-8424
1091-6490
DOI: 10.1073/pnas.1817885116
Cited by: 147
References: 10
Language: en
Licence: www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 181 d)
Funders: HHS | NIH | National Institute of Neurological Disorders and Stroke (1K08NS057824)
National Alliance for Research on Schizophrenia and Depression (Young Investigator)
HHS | NIH | National Institute of Mental Health (MH-092443, MH-094268, MH 084018, MH-105660)
HHS | U.S. Public Health Service (MH18501)

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The glutathione cycle shapes synaptic glutamate activity

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