Neuroprotective potency of anti-hyperglycemic agent 1-deoxynojirimycin

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Brain insulin resistance often precedes Alzheimer’s disease (AD) long before its onset. We thereby assessed the use of 1-deoxynojirimycin (DNJ), an aza-sugar and insulin sensitizer, to relieve AD symptoms in cell culture model of neuronal insulin resistance. By assessing the changes in insulin signaling components and AD markers, we found that DNJ: 1) reverses neuronal insulin resistance by promoting AKT/GSK3B cascade: 2) attenuates tau hyperphosphorylation by inhibiting GSK3B activity (a major tau kinase) via Ser9 phosphorylation; 3) increases the expression of insulin-degrading enzyme (Ide), which may help to clear amyloid-β and lower its accumulation. Overall, this data provides novel insight into the neuroprotective mechanism of DNJ, that is, by preserving neuronal insulin sensitivity.