Aminostyrylbenzofuran Directly Reduces Oligomeric Amyloid- beta and Reverses Cognitive Deficits in Alzheimer Transgenic Mice: e95733

• Published in: PloS one 2014-04, Vol.9 (4)
• Main 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
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0095733

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- beta 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- beta 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- beta 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.