scholarly journals Sucrose modulates insulin amyloid-like fibril formation: effect on the aggregation mechanism and fibril morphology

RSC Advances ◽  
2017 ◽  
Vol 7 (17) ◽  
pp. 10487-10493 ◽  
Author(s):  
Carlotta Marasini ◽  
Vito Foderà ◽  
Bente Vestergaard
Keyword(s):  
Human Insulin ◽  
Fibril Formation ◽  
Aggregation Mechanism ◽  
Fibril Morphology

Sucrose modifies the human insulin fibrillation pathways, affecting the fibril morphology.

scholarly journals Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity

2019 ◽  
Vol 2 (5) ◽  
pp. e201900486 ◽  
Author(s):  
Justine Lempart ◽  
Eric Tse ◽  
James A Lauer ◽  
Magdalena I Ivanova ◽  
Alexandra Sutter ◽  
...  
Keyword(s):  
Extracellular Space ◽  
Therapeutic Strategy ◽  
Neuronal Cells ◽  
Lewy Bodies ◽  
Fibril Formation ◽  
Amyloid Protein ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Fibril Morphology ◽  
Rate Limiting

The universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson’s disease. Here, we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.

Structural mechanisms of oligomer and amyloid fibril formation by the prion protein

2018 ◽  
Vol 54 (49) ◽  
pp. 6230-6242 ◽  
Author(s):  
Ishita Sengupta ◽  
Jayant B. Udgaonkar
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Aggregation Mechanism ◽  
Amyloid Fibril Formation ◽  
Structural Mechanisms

The aggregation mechanism of the prion protein is highly heterogeneous.

Rational design of an orthosteric regulator of hIAPP aggregation

2015 ◽  
Vol 51 (11) ◽  
pp. 2095-2098 ◽  
Author(s):  
De-Sheng Zhao ◽  
Yong-Xiang Chen ◽  
Yan-Mei Li
Keyword(s):  
Rational Design ◽  
Fibril Formation ◽  
Aggregation Mechanism ◽  
Toxic Oligomer

Compounds that can block hIAPP toxic oligomer but not fibril formation have been rationally designed based on the helix aggregation mechanism.

scholarly journals Collagen fibril formation in the presence of sodium dodecyl sulphate

1985 ◽  
Vol 228 (3) ◽  
pp. 551-556 ◽  
Author(s):  
G W Dombi ◽  
H B Halsall
Keyword(s):  
Conformational Changes ◽  
Sodium Dodecyl Sulphate ◽  
Collagen Fibril ◽  
Hydrophobic Interactions ◽  
Sodium Dodecyl ◽  
Distal Region ◽  
Fibril Formation ◽  
Collagen Fibrillogenesis ◽  
Fibril Morphology

Sodium dodecyl sulphate (SDS) was used to weaken both the electrostatic and the hydrophobic interactions during collagen fibrillogenesis in vitro. The rate and extent of fibril formation as well as fibril morphology were affected by SDS concentration. Both the formation of large fibrils at 0.3 mM-SDS and the complete cessation of fibril formation at 0.5 mM-SDS were considered to be the result of SDS-induced conformational changes in the non-helical telopeptides. A possible mechanism of SDS interaction with the N-terminal and the distal region of the C-terminal telopeptides is offered.

Sulfated polysaccharide ascophyllan prevents amyloid fibril formation of human insulin and inhibits amyloid-induced hemolysis and cytotoxicity in PC12 cells

2021 ◽  
Author(s):  
Yan Liang ◽  
Mikinori Ueno ◽  
Shijiao Zha ◽  
Takasi Okimura ◽  
Zedong Jiang ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Human Insulin ◽  
Amyloid Fibril ◽  
Gel Filtration ◽  
Sulfated Polysaccharide ◽  
Fibril Formation ◽  
Sulfated Polysaccharides ◽  
Structure Transition ◽  
Amyloid Fibril Formation ◽  
Α Helix

Abstract We found that ascophyllan significantly inhibited the fibrillation of human insulin, and was the most effective among the sulfated polysaccharides tested. Gel-filtration analysis suggested that ascophyllan was capable of forming a complex with insulin through a weak interaction. Secondary structure transition from native α-helix to β-sheet predominant structure of insulin under the fibrillation conditions was suppressed in the presence of ascophyllan. Interestingly, ascophyllan attenuated insulin fibrils-induced hemolysis of human erythrocytes. Moreover ascophyllan attenuated insulin amyloid induced cytotoxicity on rat pheochromocytoma PC12 cells and reduced the level of intracellular reactive oxygen species (ROS). This is the first report indicating that a sulfated polysaccharide, ascophyllan can suppress the insulin amyloid fibril formation and inhibit the fibril-induced detrimental bioactivities.

scholarly journals Mechanistic Insights into the Protective Roles of Polyphosphate Against Amyloid Cytotoxicity

2019 ◽  
Author(s):  
Justine Lempart ◽  
Eric Tse ◽  
James A. Lauer ◽  
Magdalena I Ivanova ◽  
Alexandra Sutter ◽  
...  
Keyword(s):  
Extracellular Space ◽  
Therapeutic Strategy ◽  
Neuronal Cells ◽  
Lewy Bodies ◽  
Fibril Formation ◽  
Amyloid Protein ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Fibril Morphology ◽  
Rate Limiting

ABSTRACTThe universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson’s Disease. Here we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology, and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific, and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.

Inhibition and disintegration of insulin amyloid fibrils: a facile supramolecular strategy with p-sulfonatocalixarenes

2016 ◽  
Vol 52 (14) ◽  
pp. 2992-2995 ◽  
Author(s):  
Meenakshi N. Shinde ◽  
Nilotpal Barooah ◽  
Achikanath C. Bhasikuttan ◽  
Jyotirmayee Mohanty
Keyword(s):  
Human Insulin ◽  
Therapeutic Strategy ◽  
Amyloid Fibrils ◽  
Fibril Formation

This study reveals the ability of p-sulfonatocalix[4/6]arenes to effectively inhibit the fibril formation in human insulin and demonstrate its potential to disintegrate/dissolve the mature fibrils, a promising supramolecular therapeutic strategy for amyloidosis.

scholarly journals Peptide backbone modifications of amyloid β (1–40) impact fibrillation behavior and neuronal toxicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benedikt Schwarze ◽  
Alexander Korn ◽  
Corinna Höfling ◽  
Ulrike Zeitschel ◽  
Martin Krueger ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Structural Heterogeneity ◽  
Fibril Formation ◽  
Amyloid Formation ◽  
Peptide Backbone ◽  
Hydrophobic Contact ◽  
Molecular Events ◽  
Active Research ◽  
Fibril Morphology ◽  
Almost All

AbstractFibril formation of amyloid β (Aβ) peptides is one of the key molecular events connected to Alzheimer’s disease. The pathway of formation and mechanism of action of Aβ aggregates in biological systems is still object of very active research. To this end, systematic modifications of the Phe19–Leu34 hydrophobic contact, which has been reported in almost all structural studies of Aβ40 fibrils, helps understanding Aβ folding pathways and the underlying free energy landscape of the amyloid formation process. In our approach, a series of Aβ40 peptide variants with two types of backbone modifications, namely incorporation of (i) a methylene or an ethylene spacer group and (ii) a N-methylation at the amide functional group, of the amino acids at positions 19 or 34 was applied. These mutations are expected to challenge the inter-β-strand side chain contacts as well as intermolecular backbone β-sheet hydrogen bridges. Using a multitude of biophysical methods, it is shown that these backbone modifications lead, in most of the cases, to alterations in the fibril formation kinetics, a higher local structural heterogeneity, and a somewhat modified fibril morphology without generally impairing the fibril formation capacity of the peptides. The toxicological profile found for the variants depend on the type and extent of the modification.

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