title: Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.
abstract: Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Jiao
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Xiu-Qing
authors.initials: XQ
authors.lastname: Yao
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia;
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia;
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Chi
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Shen
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Ye-Ran
authors.initials: YR
authors.lastname: Wang
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Zeng
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia;
authors.forename: Ankit
authors.initials: A
authors.lastname: Parikh
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Liang
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Xian-Le
authors.initials: XL
authors.lastname: Bu
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Juan
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650031, China;
authors.forename: Yue-Qin
authors.initials: YQ
authors.lastname: Zeng
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; and.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Xu
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia;
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
authors.forename: Hua-Dong
authors.initials: HD
authors.lastname: Zhou
authors.affiliation: School of Pharmacy and Medical Sciences and Sansom Institute, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia; Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650031, China; xin-fu.zhou@unisa.edu.au yanjiang_wang@tmmu.edu.cn.
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China; xin-fu.zhou@unisa.edu.au yanjiang_wang@tmmu.edu.cn.
authors.forename: Yan-Jiang
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002460:Cell Line; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D000077553:Edaravone; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008822:Mice, Transgenic; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D053764:Presenilin-1 / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000150:complications / Q000188:drug therapy; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D053764:Presenilin-1; D016875:tau Proteins; D000077553:Edaravone; D000983:Antipyrine
keywords: Alzheimer’s disease; BACE1; Edaravone; amyloid-β; oxidative stress
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