The association between protein aggregation and neurodegenerative diseases such as Parkinson's disease continues to be well interrogated but poorly elucidated at a mechanistic level. Nevertheless, the formation of amyloid fibrils from the destabilization and misfolding of native proteins is a molecular hallmark of disease. Consequently, there is ongoing demand for the identification and development of small molecules which prevent fibril formation. This study comprehensively assesses the inhibitory properties of two small molecules, the lignan polyphenol honokiol and the flavonoid 2',3',4'-trihydroxyflavone, in preventing α-synuclein fibrilization. The data shows that honokiol does not prevent α-synuclein fibril elongation, while 2',3',4'-trihydroxyflavone is effective at inhibiting fibril elongation and induces oligomer formation (for both wild-type α-synuclein and the disease-associated A53T mutation). Moreover, the exposed hydrophobicity of α-synuclein fibrils is reduced in the presence of 2',3',4'-trihydroxyflavone, whereas the addition of honokiol did not reduce the hydrophobicity of fibrils. In addition, ion mobility-mass spectrometry revealed that the conformation of α-synuclein wild-type and A53T monomers after disassembly is restored to a nonaggregation-prone state upon 2',3',4'-trihydroxyflavone treatment. Collectively, this study shows that the mechanisms by which these polyphenols and flavonoids prevent fibril formation are distinct by their interactions at various phases of the fibril-forming pathway. Furthermore, this study highlights how thorough biophysical interrogation of the interaction is required for understanding the ability of inhibitors to prevent protein aggregation associated with disease.
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http://dx.doi.org/10.1021/acschemneuro.0c00654 | DOI Listing |
ACS Biomater Sci Eng
January 2025
Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
Sepsis is a severe and complex systemic infection that can result in multiple organ dysfunction. Sepsis-associated acute kidney injury (SAKI), caused by inflammatory response, oxidative stress, and cellular apoptosis, is a common complication that seriously impacts patient survival rates. Herein, a potent and novel metal-polyphenol nanomicelle can be efficiently self-assembled with Pt and honokiol (HK) by the chelation, π-π conjugation, hydrophobic action, and the surfactant properties of Tween-80.
View Article and Find Full Text PDFFront Pharmacol
October 2024
Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai, China.
Cells
October 2024
Department of Neurosciences, Psychology, Drug Research and Child Health (Neurofarba), University of Floence, Viale G. Pieraccini 6, 50121 Florence, Italy.
Eur J Med Chem
June 2024
Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China. Electronic address:
Honokiol (HNK) is a typical natural biphenyl polyphenol compound. It has been proven to have a wide range of biological activities, including pharmacological effects such as anti-cancer, anti-inflammatory, neuroprotective, and antimicrobial. However, due to the poor stability, water solubility, and bioavailability of HNK, HNK has not been used in clinical treatment.
View Article and Find Full Text PDFPoult Sci
July 2024
Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, P. R. China. Electronic address:
Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying mechanisms, remain unclear. Therefore, the aim of the present study was to investigate the effects of honokiol on the growth performance, antioxidant capacity, and intestinal histomorphology of broiler chickens and to explore the underlying mechanisms.
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