Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits
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..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:112 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 112(2015), 16, Seite 5225 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Qing-Hua [VerfasserIn] |
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| Links: |
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| doi: |
10.1073/pnas.1422998112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits |
| 264 | 1 | |c 2015 | |
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| 520 | |a 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. | ||
| 540 | |a Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences | ||
| 650 | 4 | |a Antipyrine - chemistry | |
| 650 | 4 | |a Cognition Disorders - pathology | |
| 650 | 4 | |a Behavior, Animal - drug effects | |
| 650 | 4 | |a Alzheimer Disease - drug therapy | |
| 650 | 4 | |a Cognition Disorders - complications | |
| 650 | 4 | |a Antipyrine - administration & dosage | |
| 650 | 4 | |a Dendrites - pathology | |
| 650 | 4 | |a Brain - pathology | |
| 650 | 4 | |a Dendrites - drug effects | |
| 650 | 4 | |a Antipyrine - pharmacology | |
| 650 | 4 | |a Inflammation - pathology | |
| 650 | 4 | |a Phosphorylation - drug effects | |
| 650 | 4 | |a Amyloid - metabolism | |
| 650 | 4 | |a Antipyrine - analogs & derivatives | |
| 650 | 4 | |a Brain - drug effects | |
| 650 | 4 | |a Presenilin-1 - metabolism | |
| 650 | 4 | |a Amyloid beta-Peptides - toxicity | |
| 650 | 4 | |a Antipyrine - therapeutic use | |
| 650 | 4 | |a Protein Aggregation, Pathological - complications | |
| 650 | 4 | |a Neurotoxins - toxicity | |
| 650 | 4 | |a Cognition Disorders - drug therapy | |
| 650 | 4 | |a tau Proteins - metabolism | |
| 650 | 4 | |a Alzheimer Disease - pathology | |
| 650 | 4 | |a Alzheimer Disease - complications | |
| 650 | 4 | |a Protein Aggregation, Pathological - drug therapy | |
| 650 | 4 | |a Oxidative Stress - drug effects | |
| 650 | 4 | |a Protein Processing, Post-Translational - drug effects | |
| 650 | 4 | |a Diagnosis | |
| 650 | 4 | |a Health aspects | |
| 650 | 4 | |a Risk factors | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a Care and treatment | |
| 650 | 4 | |a Aged | |
| 650 | 4 | |a Research | |
| 650 | 4 | |a Oligomers | |
| 650 | 4 | |a Usage | |
| 650 | 4 | |a Older people | |
| 650 | 4 | |a Pathogenesis | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Cognitive ability | |
| 650 | 4 | |a Alzheimers disease | |
| 650 | 4 | |a Oxidation | |
| 700 | 1 | |a Xu, Juan |4 oth | |
| 700 | 1 | |a Liu, Cheng-Hui |4 oth | |
| 700 | 1 | |a Wang, Yan-Jiang |4 oth | |
| 700 | 1 | |a Zeng, Gui-Hua |4 oth | |
| 700 | 1 | |a Yao, Xiu-Qing |4 oth | |
| 700 | 1 | |a Liang, Chun-Rong |4 oth | |
| 700 | 1 | |a Wang, Ye-Ran |4 oth | |
| 700 | 1 | |a Li, Jing |4 oth | |
| 700 | 1 | |a Liu, Jia |4 oth | |
| 700 | 1 | |a Zhou, Xin-Fu |4 oth | |
| 700 | 1 | |a Zhong, Jin-Hua |4 oth | |
| 700 | 1 | |a Jiao, Shu-Sheng |4 oth | |
| 700 | 1 | |a Zhu, Chi |4 oth | |
| 700 | 1 | |a Liu, Yu-Hui |4 oth | |
| 700 | 1 | |a Xiang, Yang |4 oth | |
| 700 | 1 | |a Deng, Juan |4 oth | |
| 700 | 1 | |a Zhou, Hua-Dong |4 oth | |
| 700 | 1 | |a Bu, Xian-Le |4 oth | |
| 700 | 1 | |a Shen, Lin-Lin |4 oth | |
| 700 | 1 | |a Zeng, Yue-Qin |4 oth | |
| 700 | 1 | |a Chen, Jia |4 oth | |
| 700 | 1 | |a Parikh, Ankit |4 oth | |
| 700 | 1 | |a Zeng, Fan |4 oth | |
| 700 | 1 | |a Xu, Xiang |4 oth | |
| 700 | 1 | |a Lu, Jian-Jun |4 oth | |
| 700 | 1 | |a Xu, Hai-Wei |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d Washington, DC : NAS, 1877 |g 112(2015), 16, Seite 5225 |w (DE-627)129505269 |w (DE-600)209104-5 |w (DE-576)014909189 |x 0027-8424 |7 nnns |
| 773 | 1 | 8 | |g volume:112 |g year:2015 |g number:16 |g pages:5225 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1073/pnas.1422998112 |3 Volltext |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25847999 |
| 856 | 4 | 2 | |u http://search.proquest.com/docview/1678102459 |
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