ArticleJournal of the American Chemical Society2015
A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 71 citations in OpenAlex.
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- Alzheimer's Disease: From Molecular Mechanisms to Promising Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Leveraging heterocycle-fused 1,4-benzoquinone to design chemical modulators for both metal-free and metal-bound amyloid-β.Chemical science · 2025Article
- Multi-target-directed therapeutic strategies for Alzheimer's disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition.Chemical science · 2025Review
- CNature communications · 2023Article
- Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease.Chemical science · 2023Article
- Multipronged diagnostic and therapeutic strategies for Alzheimer's disease.Chemical science · 2022Review
- Clusterin Binding Modulates the Aggregation and Neurotoxicity of Amyloid-β(1-42).Molecular neurobiology · 2022Article
- Excited-State Intramolecular Hydrogen Transfer of Compact Molecules Controls Amyloid Aggregation Profiles.JACS Au · 2022Article
- Amyloid β structural polymorphism, associated toxicity and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2021Review
- Porphyrin-Based Tumor-Targeting Theranostic Agent: Gd-TDAP.ACS medicinal chemistry letters · 2021Article
- Expression of N-Terminal Cysteine AβBiochemistry · 2021Article
- Multiple reactivities of flavonoids towards pathological elements in Alzheimer's disease: structure-activity relationship.Chemical science · 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
- Article
- A cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and an antagonist for amylin fibrillation.Chemical science · 2019Article
- Destabilization of amyloid fibrils on interaction with MoSRSC advances · 2019Article
- Biomineralized hybrid nanoparticles for imaging and therapy of cancers.Quantitative imaging in medicine and surgery · 2018Review
- 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
17 authors at 7 institutions in 2 countries.
Funding
Abstract
Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand-peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer's disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.