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Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study
Published on: July 27, 2016
Oligomeric procyanidins inhibit insulin fibrillation by forming unstructured and off-pathway aggregates
Shaohuang Chen1, Huiting Yin1, Lei Zhang1
1State Key Laboratory of Chemical Engineering, Tianjin Key Laboratory of Membrane Science and Desalination Technology, School of Chemical Engineering and Technology, Tianjin University Tianjin 300072 China surx@tju.edu.cn.
Abstract:
β-sheet-rich amyloid fibril or aggregate accumulation has been implicated in a number of human diseases. Numerous studies demonstrate that natural polyphenols decrease the risk of degenerative diseases and inhibit in vitro amyloid formation. However, the molecular mechanism for the anti-amyloidogenesis of polyphenols is still unclear. Thus, this study investigates the effects of oligomeric procyanidins (OPCs), resveratrol, and trehalose on the amyloidogenicity of insulin via thioflavin-T (ThT) fluorescence, dynamic light scattering (DLS), circular dichroism (CD), and transmission electronic microscopy (TEM). The results demonstrate that the order of inhibitory effects on insulin amyloid fibrillation is OPCs > resveratrol > trehalose, suggesting that the polyphenolic structure is important for fibril deposition. OPCs show potent inhibitory effects at all stages of insulin fibrillation and redirect the insulin aggregation pathway via the formation of unstructured, off-pathway aggregates. These findings contribute to the development of novel anti-amyloidogenic products from naturally occurring materials.
Insights
Oligomeric procyanidins (OPCs) and resveratrol effectively inhibit insulin amyloid fibrillation by promoting off-pathway aggregation. This suggests polyphenolic structures are key for preventing degenerative disease-linked protein aggregation.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Amyloid fibril accumulation is linked to human degenerative diseases.
- Natural polyphenols show potential in preventing these diseases by inhibiting amyloid formation.
- The precise molecular mechanisms of polyphenol anti-amyloidogenesis remain unclear.
Purpose of the Study:
- To investigate the anti-amyloidogenic effects of oligomeric procyanidins (OPCs), resveratrol, and trehalose on insulin.
- To elucidate the molecular mechanisms underlying polyphenol-mediated inhibition of amyloid formation.
Main Methods:
- Thioflavin-T (ThT) fluorescence assays
- Dynamic Light Scattering (DLS)
- Circular Dichroism (CD) spectroscopy
- Transmission Electron Microscopy (TEM)
Main Results:
- The inhibitory efficacy against insulin amyloid fibrillation followed the order: OPCs > resveratrol > trehalose.
- OPCs demonstrated potent inhibition across all fibrillation stages, redirecting aggregation to unstructured, off-pathway aggregates.
- Polyphenolic structure is crucial for effective inhibition of fibril deposition.
Conclusions:
- OPCs and resveratrol exhibit significant anti-amyloidogenic properties by interfering with the insulin aggregation pathway.
- Naturally occurring polyphenols, particularly OPCs, offer a promising avenue for developing therapeutic strategies against amyloid-related diseases.
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