Oxidative Stress and Immune System Dysfunction in Autism Spectrum Disorders

Abstract

Autism Spectrum Disorders (ASDs) represent a group of neurodevelopmental disorders associated with social and behavioral impairments. Although dysfunctions in several signaling pathways have been associated with ASDs, very few molecules have been identified as potentially effective drug targets in the clinic. Classically, research in the ASD field has focused on the characterization of pathways involved in neural development and synaptic plasticity, which support the pathogenesis of this group of diseases. More recently, immune system dysfunctions have been observed in ASD. In addition, high levels of reactive oxygen species (ROS), which cause oxidative stress, are present in ASD patients. In this review, we will describe the major alterations in the expression of genes coding for enzymes involved in the ROS scavenging system, in both ASD patients and ASD mouse models. In addition, we will discuss, in the context of the most recent literature, the possibility that oxidative stress, inflammation and immune system dysfunction may be connected to, and altogether support, the pathogenesis and/or severity of ASD. Finally, we will discuss the possibility of novel treatments aimed at counteracting the interplay between ROS and inflammation in people with ASD.

Keywords: ASD; ROS; autism; immune system; inflammation.

Figure 1

Reactions required for the detoxification from reactive oxygen species (ROS). Enzymes catalyzing the major detoxification reactions are reported. Abbreviations: Fenton r.: Fenton reaction; GPx: glutathione peroxidase; GR: glutathione reductase; Mit.: mitochondrial; SOD: superoxide dismutase.

Figure 2

Genes coding for enzymes involved in the ROS scavenging system are differentially expressed in mouse models of ASD. For simplicity, the gene expression of only two genes (SOD2 and GPX3) in nine out of 14 mouse models of ASD are shown. The complete information is available in the dbMDEGA database.