title: Hopeahainol A attenuates memory deficits by targeting β-amyloid in APP/PS1 transgenic mice.
abstract: Increasing evidence demonstrates that amyloid beta (Aβ) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Aβ is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H(2)O(2)-treated PC12 cells. In this study, we reported that HopA might bind to Aβ(1-42) directly and inhibit the Aβ(1-42) aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Aβ(1-42) and Aβ-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Ye
authors.forename: Huiming
authors.initials: H
authors.lastname: Ge
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Lai
authors.initials: L
authors.lastname: Qian
authors.forename: Lingling
authors.initials: L
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Shen
authors.initials: S
authors.lastname: Ji
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.forename: Jiali
authors.initials: J
authors.lastname: Jin
authors.forename: Dening
authors.initials: D
authors.lastname: Guan
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006576:Heterocyclic Compounds, 4 or More Rings; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); C526863:hopeahainol A