title: Attenuating Aβ1-42-induced toxicity by a novel acetylcholinesterase inhibitor.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215 Ranchi, India. Electronic address: nmishra@bitmesra.ac.in.
authors.forename: N
authors.initials: N
authors.lastname: Mishra
authors.forename: D
authors.initials: D
authors.lastname: Sasmal
authors.forename: K K
authors.initials: KK
authors.lastname: Singh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007189:Indans / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology; D016707:Tissue Fixation
chemical_list: C587568:3-(anthracen-10-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazole; D016229:Amyloid beta-Peptides; D000873:Anthracenes; D002800:Cholinesterase Inhibitors; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D018727:Muscarinic Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; C075222:amyloid beta-protein (1-42); D000077265:Donepezil; D012601:Scopolamine; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase; D005978:Glutathione
keywords: 3-(anthracen-10-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazole; AChE; AD; Alzheimer’s disease; Aβ; GSH; MAO; MTDL; Multi-target-directed ligand; NP-9; PAS; S.E.M.; Scopolamine; Th-T; acetylcholinesterase; acetylcholinesterase inhibitor; amnesia; glutathione; monoamine oxidase; multi-target-directed ligand; peripheral anionic site; scanning electron microscopy; thioflavin-T; β-amyloid