TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000313735
  • Gene Name:NOS2
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:IL-21/IL-21R pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:Tyrphostin AG126
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:autism spectrum disorder
  • Tissue:tissue

Other information

  • Title:Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism
  • Journal:Neurotoxicology
  • Published:2019
  • PubMed ID:31811869
  • Abstract:Autism spectrum disorder (ASD) comprises a broad range of neurodevelopmental disorders that are associated with deficits in social interaction and communication. The tyrosine kinase inhibitor tyrphostin AG126 represents a promising therapeutic agent for several neuroinflammatory disorders. There are currently no treatments available that can improve ASD and we previously showed that AG126 treatment exerts beneficial effects on BTBR T+Itpr3tf/J (BTBR) mice, a model for autism that shows the core features of ASD; however, the immunological mechanisms and molecular targets associated with this effect were previously unclear. This study was undertaken to delineate the neuroprotective effect of AG126 on BTBR mice. Here, using this mouse model, we investigated the effects of AG126 administration on IL-21R, IL-21, IL-22, TNF-α, NOS2, STAT3, IL-27, and Foxp3 production by CD8+T cells in the spleen by flow cytometry. We further explored the mRNA and protein expression of IL-21, IL-22, IL-1β, TNF-α, NOS2, JAK1, STAT3, IL-27, and Foxp3 in brain tissue by RT-PCR, and western blotting. We found that BTBR mice treated with AG126 exhibited significant decreases in IL-21R-, IL-21-, IL-22-, TNF-α-, NOS2-, STAT3-producing, and increases in IL-27- and Foxp3-producing, CD8+T cells. Our results further demonstrated that AG126 treatment effectively decreased IL-21, IL-22, IL-1β, TNF-α, NOS2, JAK1, and STAT3, and increased IL-27 and Foxp3 mRNA and protein expression in brain tissues. Our findings suggest that AG126 elicits a neuroprotective response through downregulation of the IL-21/IL-21R and JAK/STAT pathway in BTBR mice, which could represent a promising novel therapeutic target for ASD treatment.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3