title: Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid.
abstract: Aggregated β-amyloid (Aβ) plays crucial roles in Alzheimer's disease (AD) pathogenesis, therefore blockade of Aβ aggregation is considered as a potential therapeutic target. We designed and synthesized small molecules to reduce Aβ-induced cytotoxicity by inhibiting Aβ aggregation. The small molecules were screened via ThT, MTT, and cell-based cytotoxicity assay (Aβ burden assay). Selected compounds 1c, 1d, 1e, and 1f were then investigated by evaluating their effects on cognitive impairment of acute AD mice model. Learning and memory dysfunction by injection of Aβ(1-42) was recovered by administration of these molecules. Especially, 1d showed the best recovery activity in Y-maze task, object recognition task, and passive avoidance task with dose dependent manner. These results suggest that 1d has high potential as a therapeutic agent for AD.
authors: Korea Institute of Science and Technology, 39-1 Hawolgog-dong, Seoul 136-791, Republic of Korea.
authors: Yun Suk
authors: YS
authors: Lee
authors: Hye Yun
authors: HY
authors: Kim
authors: YoungSoo
authors: Y
authors: Kim
authors: Jae Hong
authors: JH
authors: Seo
authors: Eun Joo
authors: EJ
authors: Roh
authors: Hogyu
authors: H
authors: Han
authors: Kye Jung
authors: KJ
authors: Shin
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D008970:Molecular Weight; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D001555:Benzene Derivatives; D052160:Benzothiazoles; D003373:Coumaric Acids; D010446:Peptide Fragments; D013267:Stilbenes; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T; C004999:ferulic acid; D003474:Curcumin; D000077185:Resveratrol