Gene Signalling Pathways, Putative Biomarkers and Hypothetical Modulation in Autism Spectrum Disorders
TL;DR
Integrative pathogenetic mechanisms of ASD are explored, encompassing prenatal viral exposure, alterations in serotonin and oxytocin signaling pathways, regulation of N-methyl-D-aspartate receptors, SHANK proteins, and members of the Solute Carrier protein family.
Abstract
Abstract. Autism spectrum disorder (ASD) is one of the most common neurological disorders, with a ubiquitous in-crease in prevalence. A theoretical rationale is providing for identifying potentially clinically significant diagnostic bi-omarkers and opportunities for targeted pharmacological modulation based on current data on gene signaling path-ways. This systematic review is based on data from systematic reviews and meta-analyses devoted to the basic aspects of autism spectrum disorder. This has made it possible to outline approaches to syndrome-associated diagnosis and treatment strategies. This article explores integrative pathogenetic mechanisms of ASD, encompassing prenatal viral exposure, alterations in serotonin and oxytocin signaling pathways, regulation of N-methyl-D-aspartate receptors, SHANK proteins, and members of the Solute Carrier protein family. Immune, viral, and metabolic factors, neurotrans-mitter systems, synaptic proteins and structural regulation, biomarkers, and therapeutic strategies were detected as di-agnostic and modulation promising in ASD. The potential of combined modulation involving retinoic acid derivatives, folates, antioxidants, neurotrophins, oxytocin preparations, glycine, and magnesium has been demonstrated, depending on the syndromic manifestation of ASD. A possible role of the rubella virus in prenatal disruption of retinoic acid me-tabolism and subsequent impairment of neuronal pathway formation has been demonstrated, as well as the specific in-fluence of the COVID-19 virus on the IGF-1 signaling pathway. An association has been proposed between autoimmune activation during impaired neuronal maturation and ferroptosis processes, resulting in decreased ferritin and transfer-rin levels in children with ASD. Analysis of the literature explores the potential for more selective diagnosis and modu-lation in ASD using specific biomarkers and to indicate directions for future research.