Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives.

Autor: Ermakov EA; Laboratory of Repair Enzymes, Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Novosibirsk 630090, Russia., Dmitrieva EM; Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634014, Russia., Parshukova DA; Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634014, Russia., Kazantseva DV; Siberian State Medical University, Tomsk 634055, Russia., Vasilieva AR; Siberian State Medical University, Tomsk 634055, Russia., Smirnova LP; Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634014, Russia.
Jazyk: angličtina
Zdroj: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2021 Jan 23; Vol. 2021, pp. 8881770. Date of Electronic Publication: 2021 Jan 23 (Print Publication: 2021).
DOI: 10.1155/2021/8881770
Abstrakt: Schizophrenia is recognized to be a highly heterogeneous disease at various levels, from genetics to clinical manifestations and treatment sensitivity. This heterogeneity is also reflected in the variety of oxidative stress-related mechanisms contributing to the phenotypic realization and manifestation of schizophrenia. At the molecular level, these mechanisms are supposed to include genetic causes that increase the susceptibility of individuals to oxidative stress and lead to gene expression dysregulation caused by abnormal regulation of redox-sensitive transcriptional factors, noncoding RNAs, and epigenetic mechanisms favored by environmental insults. These changes form the basis of the prooxidant state and lead to altered redox signaling related to glutathione deficiency and impaired expression and function of redox-sensitive transcriptional factors (Nrf2, NF- κ B, FoxO, etc.). At the cellular level, these changes lead to mitochondrial dysfunction and metabolic abnormalities that contribute to aberrant neuronal development, abnormal myelination, neurotransmitter anomalies, and dysfunction of parvalbumin-positive interneurons. Immune dysfunction also contributes to redox imbalance. At the whole-organism level, all these mechanisms ultimately contribute to the manifestation and development of schizophrenia. In this review, we consider oxidative stress-related mechanisms and new treatment perspectives associated with the correction of redox imbalance in schizophrenia. We suggest that not only antioxidants but also redox-regulated transcription factor-targeting drugs (including Nrf2 and FoxO activators or NF- κ B inhibitors) have great promise in schizophrenia. But it is necessary to develop the stratification criteria of schizophrenia patients based on oxidative stress-related markers for the administration of redox-correcting treatment.
Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this review.
(Copyright © 2021 Evgeny A. Ermakov et al.)
Databáze: MEDLINE
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