Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice

Sang Hyun Lee, Young Soo Kim, Hye Yun Kim, Young Hoon Kim, Maeng Sup Kim, Jae Yang Kong, Mun Han Lee, Dong Jin Kim, Young Gil Ahn

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Alzheimer's disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-βinto neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-β aggregation and ameliorates the disorder has not been approved to date. Herein, we report the effects of a potent small molecule, 6-methoxy-2-(4- dimethylaminostyryl) benzofuran (KMS88009), that directly disrupts amyloid-β oligomerization, preserving cognitive behavior when used prophylactically and reversing declines in cognitive behavior when used therapeutically. KMS88009 exhibited excellent pharmacokinetic profiles with extensive brain uptake and a high level of safety. When orally administered before and after the onset of Alzheimer's disease symptoms, KMS88009 significantly reduced assembly of amyloid-β oligomers and improved cognitive behaviors in the APP/PS1 double transgenic mouse model. The unique dual mode of action indicates that KMS88009 may be a powerful therapeutic candidate for the treatment of Alzheimer's disease.

Original languageEnglish
Article numbere95733
JournalPloS one
Volume9
Issue number4
DOIs
Publication statusPublished - 2014 Apr 23

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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