Cell Type Specific Expression of Toll-Like Receptors in Human Brains and Implications in Alzheimer’s Disease

Figure 2

TLR signaling pathways. Depending on which TLR is stimulated, adaptor proteins MyD88, TRAM, TRIF, or MAL will associate with the TIR-site of the receptor. For the MyD88-dependent pathway, MyD88 recruits phosphorylated IRAK1 or 2 and associates with TRAF6. TRAF6 forms a complex with TAB1, TAB2, TAK1, UEV1A, and UBC13. The complex formation activates TAK1 which then phosphorylates the IKK complex. Once phosphorylated it can activate transcription factors involved in JNK signaling and NF-κB which results in production of various proinflammatory cytokines. The MyD88-independent pathway is initiated by TLR3 or 4 where TRIF associates and recruits TRAF6 of TBK1. TRAF6 results in NF-κB activation and TB1 in activation of the transcription factor IRK3, producing IFNβ. TRAF6 activation can also lead to IFNα production if activated by TLR 7, 8, or 9.