Attenuating Aβ1-42-induced toxicity by a novel acetylcholinesterase inhibitor

We explored the attenuating effects of NP-9 on β-amyloid (Aβ) aggregation and amyloid-induced toxicity. NP-9 is a recently reported monoamine oxidase B (MAO-B), and acetylcholinesterase (AChE) inhibitor. In the present study, we found that NP-9 inhibited AChE activity in a dose-dependent manner with a maximal inhibition dose of 8 mg/kg, i.p. It inhibited Aβ aggregation, observed through thioflavin-T assay (IC50=60 μM) and scanning electron microscopy (S.E.M.) (no fibril formation). NP-9 has shown marked protection against scopolamine and Aβ1-42-induced memory impairments. It also minimized neuronal loss and amyloid plaque deposition in the brains of Aβ1-42-induced mice model. Therefore, NP-9 could be a promising lead molecule for AD, with effects against MAO-B, AChE, Aβ aggregation, and Aβ1-42 induced toxicity.