IRS1 and Alzheimer disease: However, some studies express divergent views on the activity of mTORC1 in AD.340 Furthermore, the increased production of inflammatory mediators like TNF-α and the activation of stress kinases such as JNK, PKR, and IKK could promote the inhibitory serine phosphorylation of IRS-1, downregulate insulin signaling in the brain, and induce AD neurological dysfunction.331,341