Aminostyrylbenzofuran Directly Reduces Oligomeric Amyloid-beta and Reverses Cognitive Deficits in Alzheimer Transgenic Mice
- Authors
- Lee, Sang-Hyun; Kim, YoungSoo; Kim, Hye Yun; Kim, Young Hoon; Kim, Maeng Sup; Kong, Jae Yang; Lee, Mun-Han; Kim, Dong Jin; Ahn, Young Gil
- Issue Date
- 2014-04-23
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.9, no.4
- Abstract
- Alzheimer's disease is an irreversible neurodegenerative disorder that is characterized by the abnormal aggregation of amyloid-beta into neurotoxic oligomers and plaques. Although many disease-modifying molecules are currently in Alzheimer clinical trials, a small molecule that inhibits amyloid-b 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-b 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-b 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.
- Keywords
- MOUSE MODEL; DISEASE; STRATEGIES; IMPAIRMENT; INHIBITORS; CASCADE; MEMORY; MOUSE MODEL; DISEASE; STRATEGIES; IMPAIRMENT; INHIBITORS; CASCADE; MEMORY
- ISSN
- 1932-6203
- URI
- https://pubs.kist.re.kr/handle/201004/126870
- DOI
- 10.1371/journal.pone.0095733
- Appears in Collections:
- KIST Article > 2014
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