Nuclear Factor Kappa B in Autism Spectrum Disorder: A Systematic Review

The nuclear factor kappa B (NF-κB) is composed of a series of transcription factors, which are involved in the expression of a plethora of target genes, many of these genes contributing to the regulation of inflammatory responses. Consistent with its central role in inflammatory responses, existing studies of the neurobiological basis for ASD propose the involvement of NF-κB in the etiology of this disorder.

The present review aimed to systematically characterize extant literatures regarding the role of NF-κB in the etiology of ASD through data derived from both human studies and animal models.

A systematic electronic search was conducted for records indexed within Pubmed, EMBASE, or Web of Science to identify potentially eligible studies. Study inclusion and data extraction was agreed by two independent authors after reviewing the abstract and full text.

Among the 371 articles identified in the initial screening, 18 articles met the eligibility criteria for this review, including 14 human case-control studies compared the expression or activation of NF-κB between ASD cases and controls as well as 4 animal studies used mouse model of ASD to examine the level of NF-κB and further evaluate its changes after different drug treatments. These included 18 studies, although relatively small in quantity, appear to support the role of NF-κB in the etiology of ASD.

Evidence generated from both human studies and animal models supported the involvement of NF-κB in the neurobiological basis of ASD, despite some concern about whether it functions as a primary contributor causes ASD onset or rather an ancillary factor regulates ASD pathogenesis. The increased understanding of NF-κB in the neurobiological basis of ASD could aid the emergence of clinically relevant diagnostic biomarkers and novel therapeutic strategies acting on the underlying disease pathogenesis. These results suggested that potential methodological differences between studies need to be accounted for and keep open the discussion over the existence of aberrantly NF-κB signaling in ASD subjects.