IRS1 and Alzheimer disease: Accordingly, Moloney et al. [40] suggested that damaged IR-associated neurotrophic and metabolic brain functions in AD neurons might arise after persistent and pathological hyperactivation of the Akt-mTOR-S6K signaling pathway, increasing IRS-1 phosphorylation at Ser312 or 616, culminating in IRS-1/2 degradation.