Dendrimer‐amyloid Aggregates Morphology and Cell Toxicity
Published:31 May 2013
D. Appelhans, N. Benseny, O. Klementiveva, M. Bryszewska, B. Klajnert, and J. Cladera, in Dendrimers in Biomedical Applications, ed. B. Klajnert, L. Peng, and V. Cena, The Royal Society of Chemistry, 2013, pp. 1-13.
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Dendrimers are branched polymeric structures that have been shown to have a promising antiamyloidogenic potential by interfering with the polymerization process leading to the formation of the amyloid aggregates related to conformational diseases, such as Alzheimer's and prion diseases. It has been established that there is a relationship between the morphology of the amyloid aggregates and the amyloid peptides or proteins toxicity: fibrillar structures present low or no toxicity, whereas oligomeric species and amorphous aggregates, the so called granular non‐fibrillar aggregates (GNAs), are toxic to cells. When interacting with the amyloid peptide associated to the onset and development of Alzheimer's disease, dendrimers can either accelerate the formation of fibrillar structures or inhibit it. Inhibition however may mean promoting the formation of amorphous aggregates. We summarize in the present chapter the experimental evidence showing that when used in a way that favors the formation and clumping of fibrils, dendrimers (glycodendrimers in particular) can reduce amyloid toxicity. However the same glycodendrimers used under different conditions can generate toxic GNAs, an aggregated form that could represent a general morphological signature for amyloid toxicity.