IRS1 and Insulin resistance: Mechanistically, AβOs may induce or exacerbate neuronal insulin resistance through the aberrant activation of the TNF-α/JNK (tumor necrosis factor α/c-Jun N-terminal kinase) pathway, leading to serine phosphorylation of IRS-1 and inducing mitochondrial oxidative stress (Kaminsky et al. 2015; Mullins et al. 2017).