Potential Role of Selenoenzymes and Antioxidant Metabolism in relation to Autism Etiology and Pathology

Abstract

Autism and autism spectrum disorders (ASDs) are behaviorally defined, but the biochemical pathogenesis of the underlying disease process remains uncharacterized. Studies indicate that antioxidant status is diminished in autistic subjects, suggesting its pathology is associated with augmented production of oxidative species and/or compromised antioxidant metabolism. This suggests ASD may result from defects in the metabolism of cellular antioxidants which maintain intracellular redox status by quenching reactive oxygen species (ROS). Selenium-dependent enzymes (selenoenzymes) are important in maintaining intercellular reducing conditions, particularly in the brain. Selenoenzymes are a family of ~25 genetically unique proteins, several of which have roles in preventing and reversing oxidative damage in brain and endocrine tissues. Since the brain's high rate of oxygen consumption is accompanied by high ROS production, selenoenzyme activities are particularly important in this tissue. Because selenoenzymes can be irreversibly inhibited by many electrophiles, exposure to these organic and inorganic agents can diminish selenoenzyme-dependent antioxidant functions. This can impair brain development, particularly via the adverse influence of oxidative stress on epigenetic regulation. Here we review the physiological roles of selenoproteins in relation to potential biochemical mechanisms of ASD etiology and pathology.

Selenium supplementation into diets containing carnosic acid, fish and rapeseed oils affects the chemical profile of whole blood in lambs

“…Se derived from dietary SeY (rich in Se-Met) is more efficiently accumulated in the animal tissues than inorganic chemical forms of Se (like SeVI or selenite) introduced via inorganic supplementation (Juniper et al, 2008). Dietary Se-Met is mainly incorporated into body proteins instead of methionine (Raymond et al, 2014). These Se-Met containing proteins are not considered as Se-proteins (Raymond et al, 2014).…”

“…Dietary Se-Met is mainly incorporated into body proteins instead of methionine (Raymond et al, 2014). These Se-Met containing proteins are not considered as Se-proteins (Raymond et al, 2014). Another study also indicates that Se-Met derived from dietary SeY is retained in tissue proteins to a greater extent than dietary Se as SeVI or selenite (Navarro-Alarcon and Cabrera-Vique, 2008).…”

Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders

“…Although these intra-cellular processes do not “pop-up” as the “usual suspect” when it comes to neuropsychiatric disorders, they have been consistently implicated in neuropsychiatric disorders such as SCZ (Prabakaran et al, 2004), BD (Baek et al, 2013), ASD (Raymond et al, 2014), and MDD (Hoyo-Becerra et al, 2014). Moreover, many psychotropic drugs seem to modulate such intra-cellular processes, adding further predictive validity to this genetic component (Lauterbach, 2013).…”

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

“…Thus, a lower level of mitochondrial reduced-glutathione (GSH, a natural antioxidant defense mechanism) existed in individuals with ASD, as compared to unaffected ones. Moreover, ASD severity has been inversely associated with GSH levels and other biological markers of cellular OS [24][25][26]. Furthermore, postmortem brain samples from ASD patients demonstrated low levels of GSH and altered activity of antioxidant-enzymes, along with clues of massive oxidative damage to proteins, enzymes and DNA, with mounting levels of lipid peroxides [26][27][28].…”