Figure 2.

Role of GSK3 in the formation of inclusion bodies. GSK3 activation leads to enhanced Abeta accumulation and hyperphosphorylation of TAU, leading to the formation of inclusion bodies, resulting in cellular stress and the activation of the unfolded protein response (UPR). In conjunction with the innate immune/stress activated kinase PKR and the UPR associated kinase PERK, this leads to the phosphorylation of eIF2α, the inhibition of general translation, IRES-mediated translation of ATF4 and the activation of the NLRP3 inflammasome, thus promoting IL-1β release and cell death.