Islet Amyloid Polypeptide

Abedini, Andisheh; Raleigh, Daniel P.

doi:10.1002/9780470572702.ch23

Cited by 2 publications

(1 citation statement)

References 146 publications

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“…Many degenerative disorders, such as Alzheimer's disease and the transthyretin amyloidoses, appear to be caused by the misassembly of protein(s) into aggregates, including amyloid fibrils . Amyloid diseases are named after the amyloid fibril deposits exhibiting a cross‐β‐sheet structure that are found in patients afflicted with these maladies .…”

Section: Introductionmentioning

confidence: 99%

Surface adsorption considerations when working with amyloid fibrils in multiwell plates and Eppendorf tubes

et al. 2013

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The accumulation of cross-b-sheet amyloid fibrils is the hallmark of amyloid diseases. Recently, we reported the discovery of amyloid disaggregase activities in extracts from mammalian cells and Caenorhabditis elegans. However, we have discovered a problem with the interpretation of our previous results as Ab disaggregation in vitro. Here, we show that Ab fibrils adsorb to the plastic surface of multiwell plates and Eppendorf tubes. This adsorption is markedly increased in the presence of complex biological mixtures subjected to a denaturing air-water interface. The time-dependent loss of thioflavin T fluorescence that we interpreted previously as disaggregation is due to increased adsorption of Ab amyloid to the surfaces of multiwell plates and Eppendorf tubes in the presence of biological extracts. As the proteins in biological extracts denature over time at the air-water interface due to agitation/shaking, their adsorption increases, in turn promoting adsorption of amyloid fibrils. We delineate important control experiments that quantify the extent of amyloid adsorption to the surface of plastic and quartz containers. Based on the results described in this article, we conclude that our interpretation of the kinetic fibril disaggregation assay data previously reported in Bieschke et al., Protein Sci 2009;18:2231-2241 andMurray et al.,

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Section: Introductionmentioning

confidence: 99%

Surface adsorption considerations when working with amyloid fibrils in multiwell plates and Eppendorf tubes

et al. 2013

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Elucidating conformational alteration of human islet amyloid polypeptide by nonsynonymous substitution

Bashar,

Barua,

Paul

et al. 2024

Preprint

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Islet amyloid polypeptide (IAPP) is a peptide hormone that serves multiple essential functions, including metabolism and regulating gastric emptying and satiation through amylin receptors. However, mutations in the IAPP, notably in the amyloidogenic segment (20-29 amino acid residues), cause its aggregation and amyloid formation, which leads to β-cell toxicity and death in type 2 diabetes mellitus (T2DM) and protein misfolding disorders (PMDs). The current work aims to elucidate the non-synonymous variants in the IAPP, which may adversely affect its function and rise to T2DM and PMDs. We harnessed in silico non-synonymous sin-gle-nucleotide polymorphisms (nsSNPs) assessment and molecular dynamics (MD) simulation to discover the potential deleterious mutants that cause T2DM and PMDs. Firstly, we executed nsSNPs prediction in IAPP using the NCBI dbSNP server, and then, all the predicted nsSNPs were assessed by a total of 26 in silico tools to find out which possessed the most deleterious effect in IAPP. Finally, MD simulation was carried out utilizing the most deleterious nsSNPs to check which significantly alters the conformational dynamics of IAPP. We found a total of 62 nsSNPs, among which the top 4 deleterious nsSNPs (T37P, L45P, G66R, and T69I) were selected based on the deleteriousness predictions by in silico tools and their location in the mature IAPP sequence (34-70 amino acid residues). MD simulations further confirm that three variants (T37P, L45P, and G66R) significantly alter the conformational dynamics of IAPP, suggesting a potential starting point for future research to elucidate the roles of these variants in IAPP aggregation and amyloid formation and their associations with T2DM and PMDs.

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Islet Amyloid Polypeptide

Cited by 2 publications

References 146 publications

Surface adsorption considerations when working with amyloid fibrils in multiwell plates and Eppendorf tubes

Surface adsorption considerations when working with amyloid fibrils in multiwell plates and Eppendorf tubes

Elucidating conformational alteration of human islet amyloid polypeptide by nonsynonymous substitution

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