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.
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