| First Author | Lee SH | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 4 | Pages | e95733 |
| PubMed ID | 24760018 | Mgi Jnum | J:217233 |
| Mgi Id | MGI:5613426 | Doi | 10.1371/journal.pone.0095733 |
| Citation | Lee SH, et al. (2014) Aminostyrylbenzofuran directly reduces oligomeric amyloid-beta and reverses cognitive deficits in Alzheimer transgenic mice. PLoS One 9(4):e95733 |
| abstractText | 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. |
