Lee, Jinny Claire Kim, Hye Yun Lee, Sejin Shin, Jisu Kim, Hyunjin Vincent Kim, Kyeonghwan Baek, Seungyeop Lee, Donghee Jeon, Hanna Kim, DaWon Yang, Seung-Hoon Han, Gyoonhee Park, Keunwan Choi, Jaeho Park, Jinwoo Moss, Jason A. Janda, Kim D. Kim, YoungSoo 2024-01-19T17:03:27Z 2024-01-19T17:03:27Z 2021-09-05 2020-07-06 1433-7851 https://pubs.kist.re.kr/handle/201004/118398 Amyloid-beta (A beta) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble A beta oligomers. Herein parallel and anti-parallel variants of A beta(1-40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized. Anti-parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and this dimer was then used in a screening platform. Through screening, two FDA-approved drugs, Oxytetracycline and Sunitinib, were identified to dissociate A beta oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated A beta in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing A beta interactions with dimer-specific molecules. English John Wiley & Sons Ltd. ALZHEIMERS-DISEASE OLIGOMERS NEURODEGENERATION INHIBITORS MECHANISM DIAGNOSIS ASSAY Discovery of Chemicals to Either Clear or Indicate Amyloid Aggregates by Targeting Memory-Impairing Anti-Parallel A beta Dimers Article 10.1002/anie.202002574 1 Angewandte Chemie International Edition, v.59, no.28, pp.11491 - 11500 Angewandte Chemie International Edition 59 28 11491 11500 scie scopus 000530663200001 2-s2.0-85085151345 Chemistry, Multidisciplinary Chemistry Article ALZHEIMERS-DISEASE OLIGOMERS NEURODEGENERATION INHIBITORS MECHANISM DIAGNOSIS ASSAY aggregation amyloid beta-peptides fluorescence high-throughput screening oligomers