Immunoglobulins G of Patients with Schizophrenia Protects from Superoxide: Pilot Results.

This study aimed to evaluate the superoxide dismutase (SOD) activity of IgG in patients with schizophrenia. After signing informed consent, we included 67 patients with schizophrenia (34 people with acute schizophrenia and 33 individuals were on outpatient treatment in therapeutic remission) and 14 healthy volunteers. IgGs from blood serum were isolated by affinity chromatography. SOD activity of antibodies was determined spectrophotometrically. We have shown for the first time that IgGs from patients with schizophrenia have SOD activity and this activity is an intrinsic property of antibodies. The maximum increase in SOD activity was registered in the group of patients in therapeutic remission compared with acute schizophrenia (p = 0.005) and in healthy individuals (p = 0.001). Based on the data of inhibitory analysis using a specific SOD inhibitor enzyme, triethylenetetramine (TETA), we can assume that the mechanism of the SOD activity of IgG is similar to the mechanism of classical enzyme catalysis. According to the kinetic analysis, the affinity of the IgGs to the substrate is higher than that of the classical SOD enzyme.

Catalytic Antibodies in Bipolar Disorder: Serum IgGs Hydrolyze Myelin Basic Protein.

The pathogenesis of bipolar affective disorder is associated with immunological imbalances, a general pro-inflammatory status, neuroinflammation, and impaired white matter integrity. Myelin basic protein (MBP) is one of the major proteins in the myelin sheath of brain oligodendrocytes. For the first time, we have shown that IgGs isolated from sera of bipolar patients can effectively hydrolyze human myelin basic protein (MBP), unlike other test proteins. Several stringent criteria were applied to assign the studied activity to serum IgG. The level of MBP-hydrolyzing activity of IgG from patients with bipolar disorder was statistically significantly 1.6-folds higher than that of healthy individuals. This article presents a detailed characterization of the catalytic properties of MBP-hydrolyzing antibodies in bipolar disorder, including the substrate specificity, inhibitory analysis, pH dependence of hydrolysis, and kinetic parameters of IgG-dependent MBP hydrolysis, providing the heterogeneity of polyclonal MBP-hydrolyzing IgGs and their difference from canonical proteases. The ability of serum IgG to hydrolyze MBP in bipolar disorder may become an additional link between the processes of myelin damage and inflammation.

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

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-κB, 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-κB 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.