DataVXACS Applied Materials & InterfacesPaper
journal article·2021-12-22Open access

Functional Gallic Acid-Based Dendrimers as Synthetic Nanotools to Remodel Amyloid-β-42 into Noncytotoxic Forms

Ana R. Araújo, Juan Correa, Vicente Dominguez-Arca, Rui L. Reis, Eduardo Fernandez-Megia, Ricardo A. Pires

ACS Applied Materials & Interfaces· Volume 13· Issue 50
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Source abstract

Abstract

The self-assembly of amyloid-β (Aβ) generates cytotoxic oligomers linked to the onset and progression of Alzheimer's disease (AD). As many fundamental molecular pathways that control Aβ aggregation are yet to be unraveled, an important strategy to control Aβ cytotoxicity is the development of bioactive synthetic nanotools capable of interacting with the heterogeneous ensemble of Aβ species and remodel them into noncytotoxic forms. Herein, the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers with a precise number of Ga at their surface is described. It is shown that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric Aβ species at their Glu, Ala, and Asp residues, promoting their remodeling into noncytotoxic aggregates in a process controlled by the Ga units. The multivalent presentation of Ga on the dendrimer surface enhances their ability to interact with Aβ, inhibiting the primary and secondary nucleation of Aβ fibrillization and disrupting the Aβ preformed fibrils.
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Research context

NanomaterialsBiomaterials

OpenAlex topics: Alzheimer's disease research and treatments · Cholinesterase and Neurodegenerative Diseases · Computational Drug Discovery Methods

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

3B’s Research Group, I3Bs − Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Portugal

ICVS/3B’s − PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal

Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, 15782 Santiago de Compostela, Spain

Biophysics and Interfaces Group, Department of Applied Physics, Faculty of Physics, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

Funding

Ministerio de Ciencia e Innovaci??n · European Regional Development Fund · Xunta de Galicia · European Social Fund · H2020 Spreading Excellence and Widening Participation

References (31)

Show source-provided references
1. 10.1038/nrdp.2015.5610.1038/nrdp.2015.56 ↗
2. 10.1126/science.156606710.1126/science.1566067 ↗
3. 10.1038/nrm381010.1038/nrm3810 ↗
4. 10.1096/fj.09-15035910.1096/fj.09-150359 ↗
5. 10.1038/s41582-018-0116-610.1038/s41582-018-0116-6 ↗
6. 10.1038/s41557-020-0452-110.1038/s41557-020-0452-1 ↗
7. 10.1038/nsb1195-99010.1038/nsb1195-990 ↗
8. 10.1111/j.1747-0285.2005.00318.x10.1111/j.1747-0285.2005.00318.x ↗
9. 10.1016/j.jmb.2012.01.01310.1016/j.jmb.2012.01.013 ↗
10. 10.1074/jbc.M50824620010.1074/jbc.M508246200 ↗
11. 10.1039/D0CC00192A10.1039/D0CC00192A ↗
12. 10.1016/j.ejmech.2014.07.11110.1016/j.ejmech.2014.07.111 ↗
13. 10.1016/j.nbd.2018.11.00910.1016/j.nbd.2018.11.009 ↗
14. 10.1002/anie.20171224410.1002/anie.201712244 ↗
15. 10.1073/pnas.160074911310.1073/pnas.1600749113 ↗
16. 10.1021/ct200196m10.1021/ct200196m ↗
17. 10.1007/s00249-011-0700-910.1007/s00249-011-0700-9 ↗
18. 10.1007/978-1-60761-744-0_210.1007/978-1-60761-744-0_2 ↗
19. 10.1039/C7CC03371K10.1039/C7CC03371K ↗
20. 10.1021/acsnano.0c0915910.1021/acsnano.0c09159 ↗
21. 10.1038/s41557-018-0023-x10.1038/s41557-018-0023-x ↗
22. 10.1016/j.jmb.2013.06.02110.1016/j.jmb.2013.06.021 ↗
23. 10.1021/ja002455u10.1021/ja002455u ↗
24. 10.1093/jac/dkq10010.1093/jac/dkq100 ↗
25. 10.1016/j.bbapap.2010.04.00110.1016/j.bbapap.2010.04.001 ↗
26. 10.1073/pnas.150085111210.1073/pnas.1500851112 ↗
27. 10.3389/fncel.2019.0030910.3389/fncel.2019.00309 ↗
28. 10.1038/srep0707410.1038/srep07074 ↗
29. 10.3390/ijms2016389610.3390/ijms20163896 ↗
30. 10.2174/156720501466617020616315810.2174/1567205014666170206163158 ↗
31. Macáková K. · 2014 · 15910.1016/B978-0-12-803961-8.50006-3 ↗