Abstract
Schizophrenia is a neurodevelopmental disorder featuring chronic, complex neuropsychiatric features. The etiology and pathogenesis of schizophrenia are not fully understood. Oxidative-antioxidant imbalance is a potential determinant of schizophrenia. Oxidative, nitrosative, or sulfuric damage to enzymes of glycolysis and tricarboxylic acid cycle, as well as calcium transport and ATP biosynthesis might cause impaired bioenergetics function in the brain. This could explain the initial symptoms, such as the first psychotic episode and mild cognitive impairment. Another concept of the etiopathogenesis of schizophrenia is associated with impaired glucose metabolism and insulin resistance with the activation of the mTOR mitochondrial pathway, which may contribute to impaired neuronal development. Consequently, cognitive processes requiring ATP are compromised and dysfunctions in synaptic transmission lead to neuronal death, preceding changes in key brain areas. This review summarizes the role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications.
Highlights
The course of schizophrenic disorders can be continuous or episodic, with progressive or permanent cognitive deficits [14]
This review summarizes the role of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia and highlights the role of a broader approach to schizophrenia by suggesting new therapeutic options
The presented mechanism becomes the cause of depolarization of mitochondrial membranes, oxidative phosphorylation disorders, and overproduction of free radicals, resulting in the exclusion of vital neurons of the frontal cortex, hippocampus, etc., which are physiologically responsible for the normal synaptic plasticity and the release of neurotransmitters [211,212,213,214]
Summary
Hydrogen peroxide reacts with methionine residues at pH = 5 to form methionine sulfoxide. Under these conditions, cysteine residues are resistant to methylation. Under the influence of glyoxal or glucose on cysteine residues, protective amino acids, peptides containing thiol groups, and proteins form. S-succinyl-cysteine is formed as a result of a nonenzymatic Michael reaction under the influence of fumaric acid on the free thiol groups of cysteine residues [157,163]. Methionine sulfoxide reductase is present in many organs, including the brain It has a protective function against the effects of oxidative stress. Various genetic variations of methionine sulfoxide reductase have been demonstrated in schizophrenic patients They may be associated with dopamine disorders and affect the effects of treatment.
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