ArticleChemistry (Weinheim an der Bergstrasse, Germany)2017
Structural and Mechanistic Insights into Development of Chemical Tools to Control Individual and Inter-Related Pathological Features in Alzheimer's Disease.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Rationally Designed Pentapeptide Analogs of Aβ19-23 Fragment as Potent Inhibitors of Aβ42 Aggregation.Molecules (Basel, Switzerland) · 2025Article
- Leveraging heterocycle-fused 1,4-benzoquinone to design chemical modulators for both metal-free and metal-bound amyloid-β.Chemical science · 2025Article
- Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation.Scientific reports · 2021Article
- Rationally designed peptide-based inhibitor of Aβ42 fibril formation and toxicity: a potential therapeutic strategy for Alzheimer's disease.The Biochemical journal · 2020Article
- Mechanistic approaches for chemically modifying the coordination sphere of copper-amyloid-β complexes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tailoring Hydrophobic Interactions between Probes and Amyloid-β Peptides for Fluorescent Monitoring of Amyloid-β Aggregation.ACS omega · 2018Article
- Minor Structural Variations of Small Molecules Tune Regulatory Activities toward Pathological Factors in Alzheimer's Disease.ChemMedChem · 2017Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
To elucidate the involvement of individual and inter-related pathological factors [i.e., amyloid-β (Aβ), metals, and oxidative stress] in the pathogenesis of Alzheimer's disease (AD), chemical tools have been developed. Characteristics required for such tool construction, however, have not been clearly identified; thus, the optimization of available tools or new design has been limited. Here, key structural properties and mechanisms that can determine tools' regulatory reactivities with multiple pathogenic features found in AD are reported. A series of small molecules was built up through rational structural selection and variations onto the framework of a tool useful for in vitro and in vivo metal-Aβ investigation. Variations include: (i) location and number of an Aβ interacting moiety; (ii) metal binding site; and (iii) denticity and structural flexibility. Detailed biochemical, biophysical, and computational studies were able to provide a foundation of how to originate molecular formulas to devise chemical tools capable of controlling the reactivities of various pathological components through distinct mechanisms. Overall, this multidisciplinary investigation illustrates a structure-mechanism-based strategy of tool invention for such a complicated brain disease.
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Registered trials
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