한빛사 논문
Jinny Claire Lee,‡[a][b] Hye Yun Kim,‡[a] Sejin Lee,‡[a][c] Jisu Shin,‡[a] Hyunjin Vincent Kim,[c] Kyeonghwan Kim,[a] Seungyeop Baek,[a][d] Donghee Lee,[a] Hanna Jeon,[a] DaWon Kim,[a] Seung-Hoon Yang,[e] Gyoonhee Han,[a][d] Keunwan Park,[f] Jaeho Choi,[g] Jinwoo Park,[g] Jason A. Moss,[b] Kim D. Janda,[b] and YoungSoo Kim*[a]
[a] Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983 (South Korea)
[b] Department of Chemistry, Department of Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla CA 92037 (USA)
[c] KIST School, University of Science and Technology (UST), Korea Institute of Science and Technology (KIST), 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 02792 (South Korea)
[d] Department of Biotechnology, Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722 (South Korea)
[e] Department of Medical Biotechnology, Dongguk University, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326 (South Korea)
[f] Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), 679, Saimdang-ro, Gangneung-si, Gangwon-do, 25451 (South Korea)
[g] BioActs, 595-9, Chungneungdaero, Namdong-gu, Incheon, 21666 (South Korea)
[‡] These authors contributed equally to this work.
*Corresponding author
Abstract
Amyloid‐β (Aβ) 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 Aβ oligomers. Herein parallel and anti‐parallel variants of Aβ(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 Aβ oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated Aβ in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing Aβ interactions with dimer‐specific molecules.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기