No abstract

Natural compounds with anti-aggregation capacity are increasingly recognized as viable candidates against neurodegenerative diseases. Recently, the polyphenolic fraction of propolis (PFP), a complex bee product, has been shown to inhibit amyloid aggregation of a model protein especially in the nanosheet form. Here, we examine the aggregation-modulating effects of the PFP nanosheets on α-synuclein (α-syn), an intrinsically disordered protein involved in the pathogenesis of Parkinson’s disease. Based on a range of biophysical data including intrinsic and extrinsic fluorescence, circular dichroism (CD) data, and nuclear magnetic resonance spectroscopy, we propose a model for the interaction of α-syn with PFP nanosheets, where the positively charged N-terminal and the middle non-amyloid component regions of α-syn act as the main binding sites with the negatively charged PFP nanosheets. The Thioflavin T (ThT) fluorescence, Congo red absorbance, and CD data reveal a prominent dose-dependent inhibitory effect of PFP nanosheets on α-syn amyloid aggregation, and the microscopy images and MTT assay data suggest that the PFP nanosheets redirect α-syn aggregation toward nontoxic off-pathway oligomers. When preformed α-syn amyloid fibrils are present, fluorescence images show co-localization of PFP nanosheets and ThT, further confirming the binding of PFP nanosheets with α-syn amyloid fibrils. Taken together, our results demonstrate the binding and anti-aggregation activity of PFP nanosheets in a disease-related protein system and propose them as potential nature-based tools for probing and targeting pathological protein aggregates in neurodegenerative diseases.