%0 Journal Article
%A Rafiei, Yasin
%A Salmani, Bahram
%A Mirzaei-Behbahani, Behnaz
%A Taleb, Mahshid
%A Meratan, Ali Akbar
%A Ramezani, Mohammad
%A Nikfarjam, Nasser
%A Becker, Stefan
%A Rezaie Ghaleh, Nasrollah
%T Polyphenols-Based Nanosheets of Propolis Modulate Cytotoxic Amyloid Fibril Assembly of α-Synuclein
%J ACS chemical neuroscience
%V 13
%N 22
%@ 1948-7193
%C Washington, DC
%I ACS Publ.
%M FZJ-2022-05902
%P 3168 - 3179
%D 2022
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 36314062
%U <Go to ISI:>//WOS:000879961600001
%R 10.1021/acschemneuro.2c00465
%U https://juser.fz-juelich.de/record/916056