Open access peer-reviewed chapter

Superoxide Dismutase in Psychiatric Diseases

Written By

Vladimir Djordjević

Submitted: 23 June 2021 Reviewed: 09 August 2021 Published: 28 April 2022

DOI: 10.5772/intechopen.99847

From the Edited Volume

Reactive Oxygen Species

Edited by Rizwan Ahmad

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As with many other human diseases, oxidative stress is implicated in many neuropsychiatric disorders, including schizophrenia, bipolar disorder, depression and Alzheimer’s disease. Due to high oxygen consumption and a lipid-rich environment, the brain is highly susceptible to oxidative stress or redox imbalance. Both increased production of reactive oxygen species and antioxidant defense disorders have been demonstrated in psychiatric patients. Superoxide dismutase (SOD) is the primary, critical enzyme in the detoxification of superoxide radicals, because they are the main ROS, primarily generated in the most biological reactions of free radical formation. There are inconsistent data on this enzyme activity in patients with different psychoses. Since psychotic disorders are complex and heterogeneous disorders, it is not surprising that different authors have found that SOD activity is increased, decreased, or unchanged in the same type of psychosis. This review examines and discusses some recent findings linking SOD activity to schizophrenia, bipolar disorder, depression and Alzheimer’s disease.


  • superoxide dismutase
  • schizophrenia
  • bipolar disorder
  • depression
  • Alzheimer’s disease

1. Introduction

More than 90% of molecular oxygen (which is essential for aerobic lifestyle) intaken in the human body is reduced into water by receiving four electrons from the electron-transport system in the respiratory chain of mitochondria. A small amount of oxygen is incorporated in biological substrates, and rest of oxygen is transformed into reactive oxygen species (ROS) that include potentially toxic oxygen free radicals [1] and very reactive non-radical species. The reduction of oxygen by one electron at a time produces superoxide anion radical (O2.−), the precursor of most ROS and a mediator in oxidative chain reactions. Superoxide is then dismutated either spontaneously or by superoxide dismutase into hydrogen peroxide (H2O2). H2O2 can be fully reduced to water or partially reduced (in a reaction catalyzed by reduced transition metals) to hydroxyl radical (OH.) which is one of the strongest oxidants in nature. Except the respiratory chain of mitochondria, enzymatic sources of superoxide production include phagocyte NADPH (nicotinamide adenine dinucleotide phosphate) oxidase, cytochrome P450−dependent oxygenases and xanthine oxidase (XO). Non-enzymatic production occurs when a single electron is directly transferred to oxygen by reduced coenzymes or prosthetic groups (flavins or iron sulfur clusters), by xenobiotics previously reduced by certain enzymes (adriamycin or paraquat), or by mitochondrial redox centres that may leak electrons to oxygen [2].

Basal cellular metabolism continuously produces ROS that occurs in endogenous sources such as mitochondria, peroxisomes, cytochrome P450, inflammatory cell activation and other cellular elements [3], but in vivo the mainly ROS production occurs within the mitochondria [4]. In physiological conditions, when the redox status is balanced, ROS are produced in appropriate levels because they are necessary and beneficial for normal physiological functions: they can protect the cell from infections [5, 6]; they play a role in the regulation of cardiac and vascular cell functioning [6]; they regulate intracellular processes such as calcium concentration, protein phosphorylation/dephosphorylation and transcription factor activation. ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), apoptosis, ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2) [7].

Maintenance of ROS at the physiological level is enabled by the antioxidant system which consists of antioxidative enzymes (superoxide dismutase, peroxidase, catalase, glutathione reductase and thioredoxin) and non-enzymatic antioxidants including reduced glutathione (GSH), vitamins (A, C, E), thiols, zinc, selenium, uric acid, albumin, bilirubin, N-acetylcysteine, and melatonin). Any disturbance of the balance between radical production and antioxidant defense (the overproduction of ROS and/or insufficiency of the antioxidant defense mechanisms) [8, 9], leads to oxidative stress and the manifestation of toxic effects of reactive species. The brain is especially sensitive to oxidative damage because it has high capacity to consume large amounts of oxygen (more than 20% of totally inhaled oxygen) that directly enhances the production of free radicals [5]; it has scarce antioxidant system; low expression of SOD, GPx and catalase; a significantly lower concentration of reduced GSH in comparison with other tisses; in some regions, the brain contains high concentrations of vitamin C and metals (e.g. iron, zinc, copper and manganese) which makes favorable conditions for the production of free radicals through the Fenton reaction; it is rich in polyunsaturated fatty acids that make it susceptible to oxidative attack. This situation is exacerbated by many factors including oxidative potential of monoamines, secondary oxidative cell damage induced by neurotoxic effects of excitotoxic amino acids (glutamate), and secondary inflammatory response. Due to the inability of neurons to produce glutathione which plays the main role in the protection of neuronal tissue from ROS [10], and in the modulation of redox-sensitive sites including NMDA receptors [11], the brain has the limited capacity to scavenge ROS. Besides, neurons are the first cells that can be affected if the concentration of ROS enhances or the concentration of antioxidants declines. Increasing body of evidence shows that partially reduced oxygen species are involved in the pathogenesis of more than hundred human diseases including psychiatric diseases such as schizophrenia, bipolar disorder, depression and Alzheimer’s disease.


2. Superoxide dismutase

Superoxide dismutase (SOD; EC is an enzyme that catalyzes the dismutation of the toxic superoxide radical, into either molecular oxygen or hydrogen peroxide, thus preventing peroxynitrite production and further damage [12]. Superoxide anion radical (O2.−) can be formed by one-electron reduction of molecular oxygen or by one-electron oxidation of hydrogen peroxide. It is highly effective in the inactivation of some enzymes, but it cannot directly oxidize unsaturated faty acids. In biological systems, it is generated accedentally via the electron transport systems in either the endoplasmic reticulum or mitochondria via electron leakage from intermediate electron carriers onto oxygen; via autooxidation of redox-active chemicals [13]; via glycation of proteins [14]; and via thiol oxidation. By various mechanisms superoxide is generated by oxidases, in particular, xanthine oxidase and NADPH oxidase of the phagocytic cells. During phagocytosis, neutrophils produce 16 times more superoxide (4.7 nmol/106 cells per minute) than that produced in resting cells [15]. The superoxide produced in this manner allows phagocytes to kill the microorganisms in the invading host. Vascular endothelial cells, fibroblasts, lymphocytes and many other human cells release superoxide involved in intracellular signaling in physiological conditions. Xanthine oxidoreductase (XOR), which has a key role in purine catabolism, may exists in two forms, xanthine oxidase (XO) and xanthine dehydrogenase (XDH). The enzyme originally exists in its XDH form, but is readily converted to XO either irreversibly by proteolysis or reversibly by oxidation of Cys residues to form disulfide bridges [16, 17]. The reoxidation of fully reduced XO yields two H2O2 and two superoxide radicals [18], which may lead to the formation more toxic reactive species. However, low concentrations of superoxide and hydrogen peroxide are initially used by the cell for the mobilization of the antioxidative system.

Since superoxide is the primary ROS produced from a variety of sources, its dismutation by SOD is of primary importance for each cell. Three forms of superoxide dismutase are present in humans: a copper- and zinc-containing superoxide dismutase (CuZnSOD/SOD1) localized predominantly in cytoplasmic and nuclear compartments as well as peroxisomes of all mammalian cells [19], a manganese superoxide dismutase (MnSOD/SOD2) localized within the mitochondrial matrix, and a copper- and zinc containing SOD predominantly found in extracellular compartments (EC SOD/SOD3). CuZnSOD present in eukaryotic cell is found sensitive to cyanide and located in the form of dimer. It may be inactivated by hydrogen peroxide, leading to the generation of either Cu (II)-OH. or its ionized form Cu (II)-O.- [20]. This enzyme can further catalyze the peroxidation of a wide vaiety of compounds.

EC SOD is homotetrameric glycoprotein whose each subunit contains a copper and zinc atom, has a high affinity for heparin sulfate and presumably scavenges superoxide that is released from the cell surface. Besides EC SOD important role in the regulation of extracellular superoxide levels, it is also important as a modulator of NO activity. EC SOD is highly expressed in blood vessels constituting up to 70% of the SOD activity in both pulmonary and systemic arteries. Its expression is mainly regulated by cytokines which increase (IFNγ) or decrease (TNFα and TGFß) EC SOD expression [21].

In eukaryotic cells MnSOD is a homotetramer located in the matrix of mitochondria. It is produced constitutively but can also be induced by cytokines (IL-1, TNF) or endotoxin [22]. In addition to cytokines, a wide range of reactive oxygen metabolites, both inducible and basal levels, may induce Mn SOD expression in distinct cell types [23] that may play a decisive role in the pathogenesis of tissue injury following oxidative stress. There are indices that transcriptional upregulation of MnSOD is mediated through the activation of nuclear transcriptional factor κB (NF- κB) by oxidants.


3. Superoxide dismutase and psychiatric diseases

3.1 Superoxide dismutase and schizophrenia

A number of studies noted increases in free radicals, alterations in antioxidant defense mechanism, increases in lipid peroxidation products and higher levels of pro-apoptotic markers in patients with neuropsychiatric disorders [24, 25, 26, 27].

One of the critical scavenging enzymes that have been reported most commonly in schizophrenia is SOD. In 1986 Abdalla et al. [28] noted that both neuroleptic-treated and untreated schizophrenic patients showed about 60% higher SOD activity than those found in control individuals. Later, elevated SOD activity in chronic schizophrenic patients has been reported in a number of studies [29, 30, 31, 32]. Djordjevic et al. [32] also showed that SOD activity was a significantly higher in patients who were younger than 34 years. These results showed that erythrocyte SOD activity is increased in the early phase of schizophrenia and may be induced in response to oxidant stress and that oxidant stress is a primary event and that SOD activity abnormalities are its consequence. That is recently confirmed by the results [33] which have shown that juvenile antioxidant treatment prevented adult deficits in a developmental model of schizophrenia. Higher conversion of superoxide might elevate hydrogen peroxide level which, in turn, could inactivate SOD [34] leading to the inhibition of the enzyme activity in the later stage of the disease. Djordjevic et al. [32] also showed that SOD activity depends on the onset of the disease, the number of psychotic episodes, the duration of the disease, and medical treatment. The authors suggested the use of antioxidants as the adjuvant therapy in the prodromal and early phase of schizophrenia. Activities of SOD and levels of malondialdehyde (MDA – commonly known as a marker of oxidative stress) in erythrocyte were significantly higher in patients with acute and chronic schizophrenia. Further, SOD activity positively correlated with scales and duration of disease while erythrocyte MDA concentration, GPx activity and GSH level were lower in patients than in controls [35]. In another study, activities of erythrocyte SOD, catalase and MDA were all greater in schizophrenics than in controls [36]. Wu et al. [31] found that both never-medicated first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first-episode schizophrenics. They also showed that SOD activity negatively correlated with positive symptoms of schizophrenia in first-episode patients. Never-treated first-episode patients had significantly higher MnSOD and total SOD activities than healthy controls, and bot enzymes showed positive correlation with depresivity and general psychopathology [37]. Increased SOD activity found in chronic medicated schizophrenic patients at baseline, decreased significantly after 45 days and 90 days of supplementation with alpha-lipoic acid [38]. Contrary to these results, decreased SOD activity has been observed in neuroleptic-naïve first-episode schizophreniform and schizophrenic patients [39]. In the study of Dadheech et al. [40] significantly lower SOD and GPx activities in schizophrenics were associated with high blood MDA levels. The condition worsened with advancing age, smoking, among literate masses and in chronic schizophrenics; whereas gender did not show any effect. However, age-dependent changes were demonstrated because it was noted a significant negative correlation between SOD activity and age [41]. A significant negative correlation was obtained between SOD activity and the duration of the schizophrenic disease [32]. In an animal model it was shown (Wistar rats) that mitochondrial SOD and GPx activities remaind unaltered between 12 and 24 months of age, with no difference between two genders, while the gender and age-differences were observed in MnSOD expression [42]. Schizophrenic patients with tardive dyskinesia (TD) showed lower plasma MnSOD activity [43], CuZnSOD activity and total antioxidant status levels, but higher MDA levels than those without TD. An increase in CuZnSOD and MnSOD in frontal cortex and substantia innominata areas of schizophrenia subjects was also observed [44]. Significantly lower SOD and catalase activities were associated with decreased GSH levels in patients with schizophrenia [45]. Among the schizophrenic patients, antioxidative enzyme activities were significantly lower in untreated patients than in the treated ones. This finding suggest that the efficacy of neuroleptics may in part be mediated by promoting an endogenous antioxidative mechanism [46]. Significantly lower SOD and GPx activities [47] did not show any difference between the three patient subgroups treated with closapine, risperidone or typical antipsychotics. Contrary, 12-week treatment with risperidone significantly decreased the initially high blood SOD levels as well as symptoms in schizophrenia [48]. Significantly lower SOD and catalase activities were also found in schizophrenic patients and their unaffected siblings compared to the control group, while GPx activity was also lower in the patient group but it was significantly higher in their unaffected siblings than in controls [49]. Moreover, a significant increase in MDA level has been found associated with significantly decreased level of vitamin C and SOD activity [50]. Meta analysis for markers of oxidative stress showed that SOD activity was significantly decreased in the disorganized type of schizophrenia patients compared to healthy controls [51]. In attempt to explain the divergence of findings related to SOD in schizophrenia, some authors have studied SOD polymorphism. However, the investigation of the functional polymorphism (Ala-9Val) in the MnSOD gene did not show any significant difference in either genotype or allele frequency between the schizophrenic and control group, nor between the polymorphism and symptom severity [52]. Another study [53] found a decrease in -9Ala (mutant) alele among patients with tardive dyskinesia, suggesting that the -9Ala (high activity) MnSOD allele may play a role in protecting against susceptibility to tardive dyskinesia in patients with schizophrenia.

The above mentioned studies showed some inconsistent results related to SOD activity which might be a consequence of several possible reasons: schizophrenia is highly heterogeneous disease; redox dysfunction may be, at least in part, state dependent; tissue-specific changes may underlie the pathophysiology [54]. Finally, there are suggesstion that the decreased level of SOD activity may have a direct implication to the oxidative stress, and that the increased enzyme levels may reflect a compensatory effect or a preceding oxidative stress in the cell [55].

3.2 Superoxide dismutase and bipolar disorder (BD)

Bipolar disorder is a highly heritable mental disorder clinically presented as unusual shifts in mood, energy and cognitive levels. It is characterized by intermittent episodes of mania or hypomania, usually interlaced with depressive episodes and these symptoms may seriously damage relationships, job or school performance, and even cause suicide. Similarly to schizophrenia, there is an increase in the number of studies related to BD and oxidative stress.

Some evidences support the role of a subtle mitochondrial compromise in BD [56]. Post-mortem studies using brain tissue of BD patients demonstrated decreased expression of mitochondrial electron transport chain genes [57] and increased levels of oxidative stress parameters [58]. The second source of oxidative stress might be hyperactivation of the glutamatergic and dopaminergic systems in BD. Glutamatergic hyperactivity leads to increased calcium influx which increases oxidative stress [59] which in turn increases glutamate [60]. The excessive dopamine production also increases oxidative stress due to the production of reactive oxygen species in dopamin metabolism [61]. Oxidative stress further induces dopamine uptake thus increasing dopamine activity in a vicious cycle. It is also showed that oxidative stress is associated with decreased γ-Aminobutyric acid release as well as with decreased serotonergic function [62].

Up now, evidence suggests elevated oxidative stress among BD patients. Several studies have reported that patients with BD have significant alterations in antioxidant enzymes, lipid peroxidation, and nitric oxide levels [63]. There is opinion that individuals who have bipolar disorder typically have lower levels of SOD and higher levels of oxidative stress as measured by nitrc oxide. After 30 day treatment SOD activity significantly increased but did not reach the control levels on the 30th day. Persistent low SOD activity might point out an oxidative imbalance in BD depressive patients and may be associated with incapacity of coping with oxidative stress [64]. However, previous studies have shown an increase in SOD activity in BD patients compared to controls [65, 66], but the phase of the disease was not taken into account in these studies. However, both SOD activity and NO level were found elevated in euthymic bipolar patients compared to controls, and NO levels significantly correlated with the total number of the manic episodes and the total number of any kind of mood episodes [67]. Increased antioxidant activity may reflect a preceding cellular oxidative stress or serve as a compensatory mechanism, and SOD may increase as a defense mechanism against increased NO levels in BD. Later, Gergerlioglu et al. [68] showed that patients in manic episode of bipolar disorder had significantly higher NO at first and 30th days after treatment, whilst at the same time SOD activities were lower than controls. At first day SOD activity was higher than at 30th day. SOD activity at 30th day is negatively correlated with the number of previous manic attacks. Contrary to these results, serum SOD activity was found significantly increased in manic and depressed BD patients as well as in schizophrenics when compared to either controls or euthymic ones. Oxidative products were also significantly higher in bipolar euthymic, bipolar manic, bipolar depressed patients and schizophrenics compared to control [69]. The results from meta-analysis recently published [70] showed a significant increase in SOD and a significant decrease in GPX in medication-free BD-mania patients compared to controls. After treatment there was no any differences in enzyme activities between patients and controls. Increased SOD+Catalase activity was observed in patients with a symptomatic affective phase of the disease but not in those with euthymia. Thus, the combination of SOD+catalase could be suggested as a state marker of affective disease, which is different in euthymia. BD patients also showed lower GSH levels and elevated oxidative stress markers. One of the reasons for the discrepancy of the results related to SOD in BD patients may be an involvement of patients in different phases of the disease. The second major drawback of the most studies was that the patients were using some drugs, such as mood stabilizers, antipsychotics and antidepressants, because it would not be appropriate to stop the treatment in these patients. Risperidone and olanzapine that are used for the treatment of schizophrenia and BD, have a secondary antioxidant benefit. In patients given these drugs SOD levels decreased [71], and levels of GSH and vitamines E and C significantly inreased [72]. Another study noted that risperidone, olanzapine and clozapine have no effect on SOD activity [73] while Li et al. [74] showed that olanzapine increases SOD activity. Later, de Sousa et al. [75] presented a reactive increase in antioxidant enzyme levels during depressive episodes in early stage BD with minimal prior treatment. Patients with BD depression showed a significant increase in catalase and GPX and no changes in SOD activity and lipid peroxidation levels. Lithium only induced a decrease in lipid peroxides and SOD levels. Both, lithium and valproate have antioxidant and antiinflammatory effects thus protecting brain cells from dysfunction and apoptosis and enhancing brain-derived neurotrophic factor [70]. Some antidepressants, like amytriptillin and venlafaxine have no effect on SOD actvivity at therapeutic doses, while in higher doses they increase SOD activity.

3.3 Superoxide dismutase and depression

Depression is a complex and heterogeneous disorder that has a negative impact on quality of life, morbidity/mortality and cognitive function. Except several mechanisms involved in its pathogenesis oxidative stress has been proposed as a contributing factor in the pathogenesis of this disease [76]. Increased levels of ROS and altered levels of antioxidant defenses have been demonstrated [77]. Significantly lower plasma concentrations of several key antioxidants (vitamin E, Zn, Koenzyme Q) as well as lower antioxidant enzyme activity have been reported in major depression. Also, an association between depression and polymorphisms in genes including manganese superoxide dismutase and catalase has been demonstrated [78]. Lower SOD activity is accompanied by increased formation of hydrogen peroxides, which can generate other ROS including the very reactive hydroxyl or metal-associated radicals [79]. However, activity of antioxidant enzymes was found controversial in patients with depression. Oxidative stress and inflammation may enhance both SOD activity and its de novo synthesis especially in early stages of an injury [80]. The meta-analysis conducted by Liu et al. [81] reported a trend toward increased SOD levels and oxidative damage products in depression and no difference in catalase activity between patients with depression and controls. SOD, nitric oxide metabolites and lipid peroxides were found significantly higher in major depressive patients than in BD or healthy controls suggesting that biomarkers related to oxidative and nitrosative stress could aid in the differentiation of major depressive disorder and BD [82]. This study also showed that there were no significant sex-linked differences in SOD or catalase activities and that education was inversely associated with SOD activity and lipid peroxides formation suggesting that education has a protective effect on the generation of ROS. Only mild association was found between nicotine dependence and increased lipid hydroperoxide levels, but not between age and measured parameters. Another study also showed a significant increase in serum SOD, serum lipid peroxides and decrease in plasma ascorbic acid levels in patients of major depression as compared to control subjects. The trend reversed significantly after treatment with fluoxetine and citalopram [83]. All of these data support the concept that depression is accompanied with elevated oxidative stress and that antidepressant treatment may reduce oxidative stress, suggesting that augmentation of antioxidant defense is one of the mechanisms underlying the neuroprotective effects of antidepressants.

3.4 Superoxide dismutase and Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the neuropathological deposition of extracellular amyloid-β peptide (Aβ) plaques and intracellular neurofibrillary tangles of hyperphosphorylated τ protein, and neurophil threads, loss of synapses and dendritic spines, cholinergic denervation, hypoperfusion and hyperemia [84, 85]. Neurofibrillary tangles mainly contain self-aggregated hyperphosphorylated tau [86]. Neurotoxic peptides of varying lengths (Aβ42, Aβ40) formed by proteolitic cleavage of amyloid beta precursor protein (APP) can also form aggregates. Accumulation in brain tissue of Aβ42 aggregates is the major pathogenetic event in Alzheimer’s disease and together with τ protein are mediators of the neurodegeneration that is among the main causative factors. Besides genetic abnormalities, oxidative stress is one of the causes of Aβ accumulation in AD. There is evidence of the leading contribution of oxidative damage to neurodegenerative disease in contrast to other diseases where oxidative stress plays a secondary role. Further, Aβ can be induced by oxidative stress [87], and in turn Aβ has the ability to induce oxidative stress. It is believed that oxidative stress occurs mainly as a result of overproduction of ROS by mitochondria.

Using the Alzheimer’s disease mouse model in combination with a mouse that overexpresses the mitochondrial SOD, Massaad et al. [88] showed that severe deficits in the spacial and associative memory of AD mice could be prevented by scavenging of superoxide. MnSOD overexpression also resulted in a reduction in Aβ plaque deposition without affecting the levels of soluble and fibrillar Aβ. This finding show that quenching mitochondrial superoxide could be a preventive approach to the occurrence of AD. On the other hand, MnSOD reduction decreased amyloid plaques in the brain parenchyma but promoted the development of cerebrovascular amyloidosis, gliosis, and plaque-independent neuritic dystrophy suggesting that MnSOD protects the aging brain against Aβ-induced impairmets [89]. In addition, CuZnSOD activity was found significantly increased in fibroblast cell lines derived from AD patients [90]. De Leoa et al. [91] showed significantly increased CuZnSOD activity in red blood cells as well as the MnSOD mRNA levels in lymphocytes of AD patients. Total SOD activity was increased, whereas total GPX, catalase and peroxiredoxin activities were decreased in the superior temporal gyrus of AD patients, suggesting that hydrogen peroxide accumulates in this brain region [92]. It was also found that higher cerebrospinal fluid (CSF) CuZnSOD correlated with better, global cognition scores, yet less gray matter, and glucose metabolism in AD-sensitive parietal and frontal regions. Higher CSF CuZnSOD also associated with more CSF total tau and phosphorylated tau-181, but not beta-amyloid 1–42 [93]. These authors hypothesized that CuZnSOD antioxidation reflects tau but not amyloid accumulation, which may lead to pro-oxidant-based neurodegeneration and cognitive dysfunction. Morever, Rs2070424 polymorphism in CuZnSOD itself might be associated with AD in Chinese han population [94]. Further, it was demonstrated that S-adenosylmethionine and SOD supplementation prevents the exacerbation of AD-like features induced by B vitamin deficiency acting synergistically. They also contrasts the amyloid deposition typically observed in TgCRND8 mice [95]. On the basis of these resulta it was suggested that the combination of S-adenosylmethionine and SOD could be carefully considered as co-adjuvant of current AD therapies.

Similarly, extensive oxidative damage has been reported in mild cognitive impairment compared to those of normal aging subjects that is confirmed by decreased plasma levels of non-enzymatic antioxidants and activity of antioxidant enzymes [96]. These results show that ROS may act as important mediators of synaptic loss and inductors of neurofibrillary tangles and senile plaques formation [97]. The accumulation of oxidatively modified biomolecules is a hallmark of brain aging and could be an early event in the progression of AD. In 2019 Kelsey McLimans said: “In individuals with Alzheimer’s or mild cognitive impairment, SOD1 was related to more gray matter, which is significant for memory. However, our results show 90 percent of this positive association is negated by tau. This bolsters our hypothesis that CuZnSOD itself isn’t detrimental; it’s just trying to limit the oxidative damage caused by tau” [98].


4. Conclusion

The biochemical characteristics and physiology of the CNS strongly suggest that the brain is susceptible to oxidative damage and that oxidative stress is part of the pathophysiological mosaic of numerous neurological and psychiatric diseases. More importantly, oxidative stress is one of several biochemical mechanisms responsible for neurodegeneration in mental disorders, which can be limited as in schizophrenia, bipolar disorder, and depression, or reflected in massive apoptosis as in Alzheimer’s disease. As the primary enzyme of antioxidant protection, SOD plays a significant role in preventing amplification of oxidative stress, production of more toxic free radicals and initiation of the internal apoptosis pathway. Although the results are inconsistent, in most studies the activity of SOD in major psychiatric illnesses has been altered. The inconsistency of the results may be a consequence of the heterogeneity of the disorders themselves, testing at different stages of the disease or the influence of psychopharmaceuticals on the enzyme activity and expression. In view of all the above, modulation of SOD activity can be considered in the light of a potential therapeutic target in major psychiatric illnesses.


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Written By

Vladimir Djordjević

Submitted: 23 June 2021 Reviewed: 09 August 2021 Published: 28 April 2022