Figure 1 Pathways affected by neuronal PTP1B activation can hasten Alzheimer's disease progression. PTP1B activity in neurons is suppressed by the endogenous inhibitor LMO4 (Pandey et al., 2013) and cellular stresses can release this inhibition by removing LMO4 from the ER to the nucleus (Chen et al., 2007; Pandey et al., 2013; Qin et al., 2015b). PTP1B can dephosphorylate and impair glutamate receptors (mGluR5 (Qin et al., 2015b)), insulin receptor (Qin et al., 2015a), leptin receptor (Pandey et al., 2013) and Ryanodine receptor 2 (RYR2) (Qin et al., 2012); these receptors and their signaling modulate synaptic plasticity and memory consolidation. mGluR5-mediated endocannabinoid (eCB) production that is important to limit anxiety can also be affected by PTP1B activation (Qin et al., 2015b). In addition, PTP1B and STEP may amplify each other's activity and STEP dephosphorylates GluN2B (aka, NR2B) (Zhang et al., 2010). ?: Putative mechanisms that remain to be tested; CICR: calcium-induced calcium release.