Our results showed that, while the beneficial effect of the positive control melatonin on AD-related pathogenesis involves the stimulation of the non-amyloidogenic pathway via both non-receptor (SIRT1) and MT1A-receptor-related ERK1/2/CREB signaling, the novel analogue 3c only attenuated memory decline via the MT1A/MT2B receptor-related ERK1/2/CREB signaling in a rat model of pin+icvAβ1-42. The gene discussed is SIRT1; the disease is Alzheimer disease.