TY  - JOUR
AU  - Rafiei, Yasin
AU  - Salmani, Bahram
AU  - Mirzaei-Behbahani, Behnaz
AU  - Taleb, Mahshid
AU  - Meratan, Ali Akbar
AU  - Ramezani, Mohammad
AU  - Nikfarjam, Nasser
AU  - Becker, Stefan
AU  - Rezaie Ghaleh, Nasrollah
TI  - Polyphenols-Based Nanosheets of Propolis Modulate Cytotoxic Amyloid Fibril Assembly of α-Synuclein
JO  - ACS chemical neuroscience
VL  - 13
IS  - 22
SN  - 1948-7193
CY  - Washington, DC
PB  - ACS Publ.
M1  - FZJ-2022-05902
SP  - 3168 - 3179
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 36314062
UR  - <Go to ISI:>//WOS:000879961600001
DO  - DOI:10.1021/acschemneuro.2c00465
UR  - https://juser.fz-juelich.de/record/916056
ER  -