IRS1 and Alzheimer disease: Microglial interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) are known activators of insulin receptor sustrate-1 (IRS-1) serine kinases (IκB kinase, c-Jun N-terminal kinase, and extracellular signal-regulated kinase-2), which decrease IRS-1 activity by phosphorylation [57] as seen in AD [58].