Potential Roles of Redox Dysregulation in the Development of Schizophrenia.

Détails

ID Serval
serval:BIB_3AABD6D2258D
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Potential Roles of Redox Dysregulation in the Development of Schizophrenia.
Périodique
Biological psychiatry
Auteur⸱e⸱s
Perkins D.O., Jeffries C.D., Do K.Q.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Statut éditorial
Publié
Date de publication
15/08/2020
Peer-reviewed
Oui
Volume
88
Numéro
4
Pages
326-336
Langue
anglais
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Résumé
Converging evidence implicates redox dysregulation as a pathological mechanism driving the emergence of psychosis. Increased oxidative damage and decreased capacity of intracellular redox modulatory systems are consistent findings in persons with schizophrenia as well as in persons at clinical high risk who subsequently developed frank psychosis. Levels of glutathione, a key regulator of cellular redox status, are reduced in the medial prefrontal cortex, striatum, and thalamus in schizophrenia. In humans with schizophrenia and in rodent models recapitulating various features of schizophrenia, redox dysregulation is linked to reductions of parvalbumin containing gamma-aminobutyric acid (GABA) interneurons and volumes of their perineuronal nets, white matter abnormalities, and microglia activation. Importantly, the activity of transcription factors, kinases, and phosphatases regulating diverse aspects of neurodevelopment and synaptic plasticity varies according to cellular redox state. Molecules regulating interneuron function under redox control include NMDA receptor subunits GluN1 and GluN2A as well as KEAP1 (regulator of transcription factor NRF2). In a rodent schizophrenia model characterized by impaired glutathione synthesis, the Gclm knockout mouse, oxidative stress activated MMP9 (matrix metalloprotease 9) via its redox-responsive regulatory sites, causing a cascade of molecular events leading to microglia activation, perineural net degradation, and impaired NMDA receptor function. Molecular pathways under redox control are implicated in the etiopathology of schizophrenia and are attractive drug targets for individualized drug therapy trials in the contexts of prevention and treatment of psychosis.
Mots-clé
Clinical high risk, Gclm KO, Glutathione, Grin2A KO, MMP9, Oxidative stress, Psychosis, Redox, Schizophrenia
Pubmed
Web of science
Création de la notice
06/07/2020 12:33
Dernière modification de la notice
16/04/2021 5:36
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