title: A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by beta-amyloid (1-42).
abstract: Inhibition of oligomeric amyloid beta (Abeta) peptide or fibril formation has emerged as a major therapeutic target for developing new drugs for Alzheimer's disease. We focused on developing inhibitors by synthesizing hybrid molecules of ferulic acid and styryl benzene, which has been known as a fibril binder. Initially, cell-based assay was carried out to evaluate the effective compound. A selected effector, 1, alleviated the Abeta-induced neuronal toxicity in differentiated SH-SY5Y human neuroblastoma cells. The effector could also inhibit Abeta fibril formation, monitored by thioflavin T fluorescence intensity assay and transmitted electron microscopic images. A strong binding affinity of 1 to non-fibrous monomer-like Abeta, which was immobilized to a surface chip, was measured using a surface plasmon resonance technique. The data suggest that the effector shifts the equilibrium of multimeric Abeta, inhibiting the pathogenic oligomer or fibril formation.
authors.affiliation: Department of Chemistry and Education, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Lee
authors.forename: Byung Hee
authors.initials: BH
authors.lastname: Shin
authors.forename: Kye Jung
authors.initials: KJ
authors.lastname: Shin
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Yu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D001554:Benzene / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004347:Drug Interactions; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D010446:Peptide Fragments / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C004999:ferulic acid; D001554:Benzene