Role of TNF-α in the Pathogenesis of Migraine

Figure 4

(a) The cycle begins with the binding of CGRP to its receptor, the CGRPR, which activates PKA (protein kinase A), which then phosphorylates the MAPK (mitogen activating protein kinase). When MAPK is phosphorylated, it causes p38 expression to increase as a result of the phosphorylation. The phosphorylated form of p38 subsequently enters the nucleus, where it stimulates the production of inflammatory genes such as TNF-α, protease. (b) After enhanced expression of protease, cleavage of mTNF-α is cleaved which after then binds with the TNFR1. Cascade of signal protein activation occurs after binding of sTNF-α to its TNFR1 which leads to the activation of IKK. IKK is responsible for the activation of NF-KB and activated form of protein enters into the nucleus and cause enhanced inflammation reaction.