Amyloid Oligomers, Protofibrils and Fibrils

Siddiqi, Mohammad Khursheed; Majid, Nabeela; Malik, Sadia; Alam, Parvez; Khan, Rizwan Hasan

doi:10.1007/978-3-030-28151-9_16

Cited by 19 publications

(13 citation statements)

References 144 publications

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“…Membrane permeabilization and calcium dyshomeostasis are the main toxicity mechanism associated with amyloid oligomers. 67 FTIR studies of Aβ42 peptides by Ha et al reported the presence of cross-β structures in Aβ42 aggregates in the presence of Fe 3+ ions, and these cross-β structures are characteristics of amyloid oligomers. 68 Through this β-sheet formation, the binding of Fe 3+ to Aβ peptides takes place and accelerates the formation of fibrillar amyloid plaques.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Probing the Role of Cu(II) Ions on Protein Aggregation Using Two Model Proteins

John

Mathew²,

Mathew

et al. 2021

ACS Omega

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Copper is an essential trace element for human biology where its metal dyshomeostasis accounts for an increased level of serum copper, which accelerates protein aggregation. Protein aggregation is a notable feature for many neurodegenerative disorders. Herein, we report an experimental study using two model proteins, bovine serum albumin (BSA) and human serum albumin (HSA), to elucidate the mechanistic pathway by which serum albumins get converted from a fully folded globular protein to a fibril and an amorphous aggregate upon interaction with copper. Steady-state fluorescence, time-resolved fluorescence studies, and Raman spectroscopy were used to monitor the unfolding of serum albumin with increasing copper concentrations. Steady-state fluorescence studies have revealed that the fluorescence quenching of BSA/HSA by Cu(II) has occurred through a static quenching mechanism, and we have evaluated both the quenching constants individually. The binding constants of BSA–Cu(II) and HSA–Cu(II) were found to be 2.42 × 10 4 and 0.05 × 10 4 M –1 , respectively. Further nanoscale morphological changes of BSA mediated by oligomers to fibril and HSA to amorphous aggregate formation were studied using atomic force microscopy. This aggregation process correlates with the Stern–Volmer plots in the absence of discernible lag phase. Raman spectroscopy results obtained are in good agreement with the increase in antiparallel β-sheet structures formed during the aggregation of BSA in the presence of Cu(II) ions. However, an increase in α-helical fractions is observed for the amorphous aggregate formed from HSA.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Probing the Role of Cu(II) Ions on Protein Aggregation Using Two Model Proteins

John

Mathew²,

Mathew

et al. 2021

ACS Omega

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“…Table 1. In vitro models of Aβ amyloid fibril formation and the associated biophysical techniques, based on the reviews of Malmos et al (2017), Bruggink et al (2012), Siddiqi et al (2019), and Kumar et al (2017) [34,[37][38][39].…”

Section: Dye-based Methodsmentioning

confidence: 99%

“…Tridimensional models of fibrils were also generated using light scattering and derived techniques, such as multiangle laser light scattering (MALLS) and dynamic light scattering (DLS). These techniques quantify the size of aggregates and allow for the monitoring of fibril formation through the detection, in real-time, of the different growing amyloid structures [37,38,55,56] (Table 1).…”

Section: Microscopy and Spectroscopy Techniquesmentioning

confidence: 99%

Deconstructing Alzheimer’s Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?

Vignon

Salvador-Prince

Lehmann

et al. 2021

IJMS

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Discovered more than a century ago, Alzheimer’s disease (AD) is not only still present in our societies but has also become the most common dementia, with 50 million people worldwide affected by the disease. This number is expected to double in the next generation, and no cure is currently available to slow down or stop the disease progression. Recently, some advances were made due to the approval of the aducanumab treatment by the American Food and Drug Administration. The etiology of this human-specific disease remains poorly understood, and the mechanisms of its development have not been completely clarified. Several hypotheses concerning the molecular mechanisms of AD have been proposed, but the existing studies focus primarily on the two main markers of the disease: the amyloid β peptides, whose aggregation in the brain generates amyloid plaques, and the abnormally phosphorylated tau proteins, which are responsible for neurofibrillary tangles. These protein aggregates induce neuroinflammation and neurodegeneration, which, in turn, lead to cognitive and behavioral deficits. The challenge is, therefore, to create models that best reproduce this pathology. This review aims at gathering the different existing AD models developed in vitro, in cellulo, and in vivo. Many models have already been set up, but it is necessary to identify the most relevant ones for our investigations. The purpose of the review is to help researchers to identify the most pertinent disease models, from the most often used to the most recently generated and from simple to complex, explaining their specificities and giving concrete examples.

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“…The number of patients with protein misfolding diseases (PMDs) is increasing rapidly [3]. Several factors, such as the lack of effective drug options, increased life expectancy, and population growth, are the reasons for increasing attention to amyloid diseases worldwide [4].…”

Section: Introductionmentioning

confidence: 99%

Mesalazine Inhibits Amyloid Formation and Destabilizes Pre-formed Amyloid Fibrils in the Human Insulin

et al. 2023

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Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis).The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy to treatments for these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin protein brillation. To induce brillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50°C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration dependent manner (different ratios (1:0.1, 1:0.5, 1:1 and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid brils and destroyed pre-formed brils. In addition, our molecular docking study con rmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our ndings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis. Highlights• Mesalazine stabilize the native state of human insulin prevents insulin brillization.• Mesalazine destabilize the pre-formed amyloid brils in a concentration-dependent manner.• Mesalazine can be proposed as a candidate for the treatment of amyloid diseases

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Amyloid Oligomers, Protofibrils and Fibrils

Cited by 19 publications

References 144 publications

Probing the Role of Cu(II) Ions on Protein Aggregation Using Two Model Proteins

Probing the Role of Cu(II) Ions on Protein Aggregation Using Two Model Proteins

Deconstructing Alzheimer’s Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?

Mesalazine Inhibits Amyloid Formation and Destabilizes Pre-formed Amyloid Fibrils in the Human Insulin

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