Hopeahainol A attenuates memory deficits by targeting β‐amyloid in APP/PS1 transgenic mice |
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Authors: | Xiaolei Zhu Lan Ye Huiming Ge Ling Chen Nan Jiang Lai Qian Lingling Li Rong Liu Shen Ji Su Zhang Jiali Jin Dening Guan Wei Fang Renxiang Tan Yun Xu |
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Affiliation: | 1. Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, , Nanjing, China;2. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, , Nanjing, China;3. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, , Nanjing, China;4. Department of Physiology, Nanjing Medical University, , Nanjing, China;5. Department of Traditional Chinese Medicine, Shanghai Institute of Food & Drug Controls, , Shanghai, China |
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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 H2O2‐treated PC12 cells. In this study, we reported that HopA might bind to Aβ1–42 directly and inhibit the Aβ1–42 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 Aβ1–42 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. |
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Keywords: | Aβ ‐binding alcohol dehydrogenase β ‐amyloid hopeahainol A neuroprotection |
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