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

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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. © 2014 Lee et al.

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Lee, S. H., Kim, Y. S., Kim, H. Y., Kim, Y. H., Kim, M. S., Kong, J. Y., … Ahn, Y. G. (2014). Aminostyrylbenzofuran directly reduces oligomeric amyloid-β and reverses cognitive deficits in Alzheimer transgenic mice. PLoS ONE, 9(4). https://doi.org/10.1371/journal.pone.0095733

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