NF-𝜿B Signaling in the Brain of Autistic Subjects

Figure 6

NF-𝜅B signal transduction pathway. NF-𝜅B heterodimer between p65 and p50/52 proteins is located in the cytosol complexed with the inhibitory protein I𝜅B𝛼. Through the intermediacy of integral membrane receptors, a variety of extracellular signals (like TNF𝛼 or growth factor BDNF) can activate the enzyme I𝜅B kinase (IKK, consisting of Ikk𝛼, 𝛽, and 𝛾) via TAK1 or PI3K/Akt, respectively. IKK, in turn, phosphorylates the I𝜅B𝛼 protein, which results in dissociation of I𝜅B𝛼 from NF-𝜅B and eventual degradation by the proteosome. The activated NF-𝜅B is then translocated into the nucleus where it binds to specific sequences of DNA called response elements and initiates the gene transcription.