Biomaterials, Biodegradables and Biomimetics Research Group

Comunications - Poster

Gallic acid-based dendrimers modulate Aβ42 fibrillization and reduces cellular toxicity


Alzheimer's disease (AD) is characterized by the occurrence of extracellular senile plaques of aggregated amyloid-beta peptide (Ab42). These plaques are generated by the self-assembling of Ab42 monomers into supramolecular nanofibrillar structures stabilized by the peptide’s β-sheets. While the senile plaques are a hallmark of AD, the presence of intracellular soluble Ab42 oligomers (precursors of the senile plaques) are reported to be the main cause of its toxicity [1]

We have previously demonstrated that the use of natural polyphenols can rescue cell viability affected by the Ab42 fibrillization. In fact, the use of EGCG as a modulator of Ab42 self-assembly has been studied, and its ability to block the assembly process has been reported [2]. The activity of EGCG is reported to occur through the interference of the Pi-Pi stacking within the Ab42 supramolecular arrangement [3]. In general, most of the natural polyphenols reported to modulate Ab42 self-assembly present galloyl-type moieties. Based on this observation, we designed dendrimers displaying this type of moieties on their surface and tested them for their ability to modulate Ab42 fibrillization.

We synthesised a G0-GA core dendrimer with two gallates, and a G1-GA one with six gallate groups. We used CD, DLS and fluorescence spectroscopy to evaluate their ability to inhibit Ab42 fibrillization. Our results show that G1-GA is able to decrease the β-sheet content of the Ab42 supramolecular assemblies, while reducing the size of the fibrils. We also confirmed that G1-GA has the capacity of maintain SH-SY5Y cell viability, reducing the oligomeric Aβ42 assemblies in the cytoplasm of the cells. Our results demonstrate that G1-GA dendrimer represents a promising custom-made nanotherapeutical tool able to modulate the toxicity of Ab42 assemblies in the AD context.




1.            Eisele, Y.S., et al., Targeting protein aggregation for the treatment of degenerative diseases. Nat Rev Drug Discov, 2015. 14(11): p. 759-780.

2.            Meisl, G., et al., Molecular mechanisms of protein aggregation from global fitting of kinetic models. Nat. Protocols, 2016. 11(2): p. 252-272.

3.            Attar, A., F. Rahimi, and G. Bitan, Modulators of Amyloid Protein Aggregation and Toxicity: Egcg and Clr01. Translational Neuroscience, 2013. 4(4): p. 385-409.

2018 TERMIS World Congress
alzheimer disease, Dendrimers, gallic acid
Open Access
Peer Reviewed
Year of Publication
Date Published
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