Kim, Young Soo Lee, Ji Hoon Ryu, Jiyeon Kim, Dong Jin 2024-01-20T22:02:06Z 2024-01-20T22:02:06Z 2021-09-03 2009-02 1381-6128 https://pubs.kist.re.kr/handle/201004/132772 Ligands selectively targeting beta-amyloid in the living brain are promising candidates of therapeutics and early diagnosis tools for Alzheimer's disease. Among the major stages of beta-amyloid aggregation, monomers and oligomers are excellent targets to reduce neurotoxic brain damages for prevention of the disease progression, while oligomers and fibrils, abundant in the late stage of the disease, are pathological objectives to develop reliable imaging probes. So far, there have been many efforts to develop a wide variety of monovalent beta-amyloid ligands such as thioflavin T, PIB, FDDNP, curcumin, and tramiprosate. However, pathology of Alzheimer's disease is not fully understood yet so that there is currently no cure and further investigations on Alzheimer's disease are needed. For past several years, multivalent beta-amyloid ligands have offered an alternative route by enhancing binding affinity of drug candidates. In addition, it has been revealed that not only neurotoxicity due to the protein misfolding but also other factors are involved in the beta-amyloid cascade such as oxidative stress, inflammation, metal chelation, and several types of neurotransmitters. Thus, there have been numerous studies to improve binding affinities of single beta-amyloid ligands via adopting multivalent effects or to develop drug candidates targeting multiple stages of the pathological cascade. In this review, multivalent and multifunctional amyloid ligands and their promising aspects as an alternative approach to Alzheimer's disease are discussed. English BENTHAM SCIENCE PUBL LTD RANDOMIZED CONTROLLED-TRIAL TARGET-DIRECTED LIGANDS HIGH BINDING-AFFINITY ALZHEIMER A-BETA IN-VIVO FIBRIL FORMATION OXIDATIVE STRESS ACETYLCHOLINESTERASE INHIBITORS SHEET BREAKER MOUSE MODEL Multivalent & Multifunctional Ligands to beta-Amyloid Article 10.2174/138161209787315648 1 CURRENT PHARMACEUTICAL DESIGN, v.15, no.6, pp.637 - 658 CURRENT PHARMACEUTICAL DESIGN 15 6 637 658 scie scopus 000263963700005 2-s2.0-65549161050 Pharmacology & Pharmacy Pharmacology & Pharmacy Review RANDOMIZED CONTROLLED-TRIAL TARGET-DIRECTED LIGANDS HIGH BINDING-AFFINITY ALZHEIMER A-BETA IN-VIVO FIBRIL FORMATION OXIDATIVE STRESS ACETYLCHOLINESTERASE INHIBITORS SHEET BREAKER MOUSE MODEL beta-Amyloid A beta multivalent multifunction ligand Alzheimer&apos s disease AD drug imaging probe early diagnosis