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 2024-01-20T10:01:37Z 2024-01-20T10:01:37Z 2021-09-05 2014-04-23 1932-6203 https://pubs.kist.re.kr/handle/201004/126870 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. English PUBLIC LIBRARY SCIENCE MOUSE MODEL DISEASE STRATEGIES IMPAIRMENT INHIBITORS CASCADE MEMORY Aminostyrylbenzofuran Directly Reduces Oligomeric Amyloid-beta and Reverses Cognitive Deficits in Alzheimer Transgenic Mice Article 10.1371/journal.pone.0095733 1 PLOS ONE, v.9, no.4 PLOS ONE 9 4 scie scopus 000335298200083 2-s2.0-84899720596 Multidisciplinary Sciences Science & Technology - Other Topics Article MOUSE MODEL DISEASE STRATEGIES IMPAIRMENT INHIBITORS CASCADE MEMORY