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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.
AuthorsShu-Sheng Jiao, Xiu-Qing Yao, Yu-Hui Liu, Qing-Hua Wang, Fan Zeng, Jian-Jun Lu, Jia Liu, Chi Zhu, Lin-Lin Shen, Cheng-Hui Liu, Ye-Ran Wang, Gui-Hua Zeng, Ankit Parikh, Jia Chen, Chun-Rong Liang, Yang Xiang, Xian-Le Bu, Juan Deng, Jing Li, Juan Xu, Yue-Qin Zeng, Xiang Xu, Hai-Wei Xu, Jin-Hua Zhong, Hua-Dong Zhou, Xin-Fu Zhou, Yan-Jiang Wang
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 16 Pg. 5225-30 (Apr 21 2015) ISSN: 1091-6490 [Electronic] United States
PMID25847999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amyloid
  • Amyloid beta-Peptides
  • Neurotoxins
  • Presenilin-1
  • tau Proteins
  • Edaravone
  • Antipyrine
Topics
  • Administration, Oral
  • Alzheimer Disease (complications, drug therapy, pathology)
  • Amyloid (metabolism)
  • Amyloid beta-Peptides (toxicity)
  • Animals
  • Antipyrine (administration & dosage, analogs & derivatives, chemistry, pharmacology, therapeutic use)
  • Behavior, Animal (drug effects)
  • Brain (drug effects, pathology)
  • Cell Line
  • Cognition Disorders (complications, drug therapy, pathology)
  • Dendrites (drug effects, pathology)
  • Edaravone
  • Humans
  • Inflammation (pathology)
  • Mice, Transgenic
  • Neurotoxins (toxicity)
  • Oxidative Stress (drug effects)
  • Phosphorylation (drug effects)
  • Presenilin-1 (metabolism)
  • Protein Aggregation, Pathological (complications, drug therapy)
  • Protein Processing, Post-Translational (drug effects)
  • tau Proteins (metabolism)

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