Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer’s Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation

Figure 5

Schematic showing the inflammation-associated mechanisms in tau phosphorylation and tangle formation in brain: environmental factors, injury to brain, or enhanced inflammation induce Aβ generation as well as microglial activation which leads to increased generation of IL-1β (cytokine) which in turn has been shown to enhance ACT expression. ACT has been shown to induce tau hyperphosphorylation through activation of GSK-3α β, or ERK (earlier studies) or JNK (data presented here). This may lead to enhanced tangle formation and neurodegeneration. ACT already has been shown to enhance Aβ aggregation and accelerated plaque formation, whether it enhances tau aggregation and tangle formation needs to be determined.