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A study employing a different dipeptidylpeptidase-4 inhibitor, linagliptin, following Aβ42 injection to brain ameliorated cognitive impairment, attenuated levels of Aβ42 oligomers, decreased the degree of insulin resistance (by decreasing levels of phosphorylation of the inhibitory Ser307 site on IRS-1), and diminished levels of GSK-3β and proinflammatory cytokines and, importantly, decreased levels of oxidative and nitrosative damage in hippocampus
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Given that NNMT has been reported to be a primary metabolic enzyme[36] and a major clearance pathway for intracellular NA,[15] it is likely that these small molecules are directly and selectively inhibiting the conversion of NA to 1-MNA