title: Neuroprotective Effect of Osthole on Neuron Synapses in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9.
abstract: Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). It has been reported that osthole exerts its neuroprotective effect on neuronal synapses, but its exact mechanism is obscure. Recently, microRNAs have been demonstrated to play a crucial role in inducing synaptotoxicity by Aβ, implying that targeting microRNAs could be a therapeutic approach of AD. In the present study, we investigated the neuroprotective effects of osthole on a cell model of AD by transducing APP695 Swedish mutant (APP695swe, APP) into mouse cortical neurons and human SH-SY5Y cells. In this study, the cell counting kit CCK-8, apoptosis assay, immunofluorescence analysis, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction, and Western blot assay were used. We found that osthole could enhance cell viability, prevent cell death, and reverse the reduction of synaptic proteins (synapsin-1, synaptophysin, and postsynaptic density-95) in APP-overexpressed cells, which was attributed to increases in microRNA-9 (miR-9) expression and subsequent decreases in CAMKK2 and p-AMPKα expressions. These results demonstrated that osthole plays a neuroprotective activity role in part through upregulating miR-9 in AD.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Interventional Therapy, Dalian Municipal Central Hospital, Dalian, Liaoning, 116033, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Engineering, University of Oxford, Oxford, OX1 3LZ, UK.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Kong
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
authors.forename: Guangxian
authors.initials: G
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, 116600, China. jingxian__yang@163.com.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D003374:Coumarins; D020662:Guanine Nucleotide Exchange Factors; D035683:MicroRNAs; D018696:Neuroprotective Agents; C504474:Psd protein, mouse; D016704:Synapsins; D016708:Synaptophysin; D011494:Protein Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D000091162:AMP-Activated Protein Kinase Kinases; C046627:osthol
keywords: Alzheimer’s disease; Amyloid precursor protein; CAMKK2–AMPK pathway; Neuron synapses; Osthole; miR-9