Cosolvent effects on the growth of amyloid fibrils

Reddy, Gunda; Muttathukattil, Aswathy N.; Mondal, Balaka

doi:10.1016/j.sbi.2019.12.011

Cited by 7 publications

(3 citation statements)

References 77 publications

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“…By contrast, high doses (>500 mM) of trehalose induce conformational transitions towards β-sheet rich hIAPP structures that seed hIAPP fibril growth 566 . This behaviour has been observed for other osmolytes 567,568 and is in accordance with the hypothesis that low concentrations of trehalose may replace water molecules close to hIAPP, bind the peptide chain through a hydrogen bond network, reduce protein-protein interactions, and eventually delay fibril growth. By contrast, at high concentrations trehalose molecules may self assemble to form clusters that, acting as crowding agents, could seed hIAPP fibrillation.…”

Section: Trehalosesupporting

confidence: 89%

Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes

et al. 2021

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The possible link between hIAPP accumulation and β-cell death in diabetic patients has inspired numerous studies focusing on amyloid structures and aggregation pathways of this hormone. Recent studies have reported on the importance of early oligomeric intermediates, the many roles of their interactions with lipid membrane, pH, insulin and zinc on the mechanism of aggregation of hIAPP. weight reduction was observed. In a phase-1 clinical trial in which AM833 was combined with the GLP-1-agonist Semaglutid, 20 weeks of treatment, participants lost an average of 17.1 % body weight. Overweight and obesity are risk factors for T2D and cardiovascular disease and the presented weight loss exceed reductions observed for GLP-1 and metformin. It should be noted that an IAPP derivative, pramlintide (symlin) is used, in addition to insulin, in patients with insulindependent T1D and T2D that have been difficult to regulate with insulin by a single drug. 42 Cross-correlation with other diseasesEpidemiological studies link diabetes with neurodegenerative diseases, including Alzheimer's disease [43][44][45][46] and Parkinson's disease. [47][48][49] The link is unclear, but the three conditions are multifactorial and have protein aggregation in their pathophysiology in common. If protein aggregation constitutes the link between these diseases, however, still needs to be proven. The Rotterdam study 50 , published in 1999, showed that patients with T2D have an almost doubled risk of developing dementia and Alzheimer's disease (AD). Data from the ULSAM study (Uppsala Longitudinal study of adult men) showed that already a moderate disturbance in the first-phase insulin release at the age of 55 increased the risk of developing AD thirty years later. 51 This suggests that diabetes precedes AD. In fact, another type of diabetes has been proposed [52][53][54] , which is type 3 diabetes (T3DM) which is an AD associated insulin resistance, also described as "brain diabetes phenotype". A considerable number of biophysical studies have shown a close link between the amyloid-forming proteins IAPP and Aβ. [55][56][57][58] IAPP immunoreactivity is present in formic acid brain extracts from patients with AD 59 and exhibited pattern on the western blot ranges from dimers to 16 mers. 60 The laddering pattern suggests that IAPP is present in the Aβ amyloid deposit. Proximity ligation assay (PLA) using two primary antibodies can be applied to determine the co-deposition of proteins. The positive PLA signal obtained after the combination of anti-IAPP and anti-Aβ antibodies points to the co-deposition of IAPP and Aβ in vivo. To confirm that the peptides interact in vivo, hIAPP transgenic mice were injected with preformed fibrils of Aβ followed by high-fat feeding for ten months. 60 Mice injected with preformed Aβ fibrils developed amyloid in 15% of the islets, which is comparable to mice injected with preformed fibrils of proIAPP. In mice injected with preformed IAPP fibrils, IAPP amyloid was found in 24 % of the islets. Control mice injected with fib...

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Section: Trehalosesupporting

confidence: 89%

Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes

et al. 2021

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“…This is supported by a high diversity of sequences and structural properties of proteins known to form amyloids, and suggests that the formation of amyloid fibers is a self‐assembly phenomenon inherently dependent on a polypeptide backbone and to lesser extend on side‐chains . Various conditions are associated with protein misfolding and aggregation into amyloids, such as denaturing conditions (acidic pH, presence of chaotrops and surfactants), presence of transition metals (e.g., Cu 2+ ) or organic solvents . These factors may induce conformations in folded or intrinsically disordered proteins that are predisposed for aggregation.…”

Section: Introductionmentioning

confidence: 99%

Aggregation and Amyloidogenicity of the Nuclear Coactivator Binding Domain of CREB‐Binding Protein

García

Giorgiutti

Khoury

et al. 2020

Chemistry A European J

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The nuclear coactivator binding domain (NCBD) of transcriptional co-regulator CREB-binding protein (CBP) is an example of conformationallym alleable proteins that can bind to structurally unrelated protein targets and adopt distinct folds in the respective protein complexes. Here, we show that the folding landscape of NCBD contains an alternative pathwayt hat resultsi np rotein aggregation and selfassembly into amyloid fibers. The initial steps of such protein misfolding are driven by intermolecular interactions of its N-terminal a-helix bringing multiple NCBD molecules into contact. These oligomers then undergo slow but progressive interconversion into b-sheet-containing aggregates.T o reveal the concealed aggregation potentialo fN CBD we used ac hemically synthesized mirror-image d-NCBD form. The addition of d-NCBD promoted self-assembly into amyloid precipitates presumably due to formation of thermodynamically more stable racemic b-sheet structures. The unexpecteda ggregation of NCBD needs to be taken into considerationg iven the multitude of protein-protein interactions and resulting biological functions mediated by CBP.

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“…Small organic molecules called osmolytes are naturally used as one of the factors counteracting cellular stress, which can lead to protein denaturation or misfolding. Much research has been undertaken to study the influence of osmolytes on protein stability [21][22][23][24][25]. Urea is the one that is usually mentioned as a typical destabilizer, and TMAO (trimethylamine Noxide) is known as one of the strongest protectants [26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Hydration of Simple Model Peptides in Aqueous Osmolyte Solutions

Panuszko

Pieloszczyk

Kuffel

et al. 2021

IJMS

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The biology and chemistry of proteins and peptides are inextricably linked with water as the solvent. The reason for the high stability of some proteins or uncontrolled aggregation of others may be hidden in the properties of their hydration water. In this study, we investigated the effect of stabilizing osmolyte–TMAO (trimethylamine N-oxide) and destabilizing osmolyte–urea on hydration shells of two short peptides, NAGMA (N-acetyl-glycine-methylamide) and diglycine, by means of FTIR spectroscopy and molecular dynamics simulations. We isolated the spectroscopic share of water molecules that are simultaneously under the influence of peptide and osmolyte and determined the structural and energetic properties of these water molecules. Our experimental and computational results revealed that the changes in the structure of water around peptides, caused by the presence of stabilizing or destabilizing osmolyte, are significantly different for both NAGMA and diglycine. The main factor determining the influence of osmolytes on peptides is the structural-energetic similarity of their hydration spheres. We showed that the chosen peptides can serve as models for various fragments of the protein surface: NAGMA for the protein backbone and diglycine for the protein surface with polar side chains.

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Cosolvent effects on the growth of amyloid fibrils

Cited by 7 publications

References 77 publications

Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes

Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes

Aggregation and Amyloidogenicity of the Nuclear Coactivator Binding Domain of CREB‐Binding Protein

Hydration of Simple Model Peptides in Aqueous Osmolyte Solutions

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