Figure 2.

Inflammatory cytokines initiate the activation of the PI3K (phosphoinositide 3 kinase) pathway, phosphorylate the JAK-STAT (Janus kinases, signal transducer and activator of transcription proteins) factors, which activate the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway and enhance the production of ROS leading to apoptosis. p38 MAPK (a mitogen-activated protein kinase) is involved in the AD mechanism which includes the cytokine activation of p38 MAPK in microglia, leads to the increased production of proinflammatory cytokines which initiates the inflammatory process, and the cytokines also initiate the activation of p28 MAPK in astrocytes and neurons, which further escalates the inflammation. All these events lead to hyperphosphorylation, inhibition of long-term potentiation, apoptosis and synaptic dysfunction. NF-кB is a regulated transcription factor, involved in the regulation of inflammation, cellular growth, immune function and apoptosis. Free radical production led to the activation of IKB which phosphorylates the NFкB inhibitor, initiates the proteasomal degradation of IKB (IkappaB kinase) and the liberation of NFкB which translocates into the nucleus and binds to the DNA responsive element. Together with the coadjuvant and other activators, the increased expression of proinflammatory cytokines is triggered and neuroinflammation is supported, which causes the degeneration of neurons and eventually leads to the progression of AD (created with http://BioRender.com/).