4.5 Article

ATTENUATING Aβ1-42-INDUCED TOXICITY BY A NOVEL ACETYLCHOLINESTERASE INHIBITOR

Journal

NEUROSCIENCE
Volume 250, Issue -, Pages 309-319

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2013.07.014

Keywords

acetylcholinesterase inhibitor; beta-amyloid; amnesia; Alzheimer's disease; Scopolamine; Multi-target-directed ligand

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Funding

  1. University Grants Commission, India

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We explored the attenuating effects of NP-9 on beta-amyloid (A beta) 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 A beta aggregation, observed through thioflavin-T assay (IC50 = 60 mu M) and scanning electron microscopy (S.E.M.) (no fibril formation). NP-9 has shown marked protection against scopolamine and A beta(1-42)-induced memory impairments. It also minimized neuronal loss and amyloid plaque deposition in the brains of A beta(1-42)-induced mice model. Therefore, NP-9 could be a promising lead molecule for AD, with effects against MAO-B, AChE, A beta aggregation, and A beta(1-42) induced toxicity. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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