Anti-Amyloidogenic and Fibril-Disaggregating Potency of the Levodopa-Functionalized Gold Nanoroses as Exemplified in a Diphenylalanine-Based Amyloid Model

Abstract

The phenomenon of proteins/peptide assembly into amyloid fibrils is associated with various neurodegenerative and age-related human disorders. Inhibition of the aggregation behavior of amyloidogenic peptides/proteins or disruption of the pre-formed aggregates is a viable therapeutic option to control the progression of various protein aggregation-related disorders such as Alzheimer's disease (AD). In the current work, we investigated both the amyloid inhibition and disaggregation proclivity of levodopa-functionalized gold nanoroses (GNRs) against various peptide-based amyloid models, including the amyloid beta peptide [Aβ (1-42) and Aβ (1-40)] and the dipeptide phenylalanine-phenylalanine (FF). Our results depicted the anti-aggregation behavior of the GNR toward FF and both forms of Aβ-derived fibrils. The peptides demonstrated a variation in their fiber-like morphology and a decline in thioflavin T fluorescence after being co-incubated with the GNR. We further demonstrated the neuroprotective effects of the GNR in neuroblastoma cells against FF and Aβ (1-42) fiber-induced toxicity, exemplified both in terms of regaining cellular viability and reducing production of reactive oxygen species. Overall, these findings support the potency of the GNR as a promising platform for combating AD.