IRS1 and Insulin resistance: Moreover, a growing body of evidence implicates brain insulin deficiency and/or insulin resistance as a key pathognomic phenomenon in both AD and PD, as indicated by the reduced expression of insulin (mRNA and protein), insulin receptors, decreased receptor affinity and reduction in the downstream signalling pathways (i.e., insulin receptor substrate 1, IRS1; phospho-AKT and phospho-glycogen synthase kinase 3β) [172,173,174,175,176,177,178,179].