The initial stage of structural transformation of Aβ42 peptides from the human and mole rat in the presence of Fe2+ and Fe3+: Related to Alzheimer's disease

Vahed, Mohammad; Sweeney, Aaron; Shirasawa, Hiroshi; Vahed, Majid

doi:10.1016/j.compbiolchem.2019.107128

Cited by 15 publications

(8 citation statements)

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“…About Aβ 1-42, Fe 3+ binds between Glu22 and the carboxyl group of the Ala42 at C-terminus. Fe2 + and Fe 3+ cause aggregation of Aβs (Azimi and Rauk 2012;Roy et al, 2020;Ryu et al, 2008;Vahed et al, 2019) (Figure 5). An increase in the iron level led to an increase in both Aβ oligomers, and Congo red was used to stain the brain for amyloid-beta plaques (House et al, 2004;Guo et al, 2013;Becerril-Ortega et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Naringin Chelates Excessive Iron and Prevents the Formation of Amyloid-Beta Plaques in the Hippocampus of Iron-Overloaded Mice

2021

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Metal chelating agents are antioxidant agents, which decrease the reductive potential and stabilize the oxidized metal ion form. In this study, we evaluated the naringin capacity in chelating iron and preventing amyloid-beta plaque formation in the hippocampus of iron-overloaded mice. Thirty-five NMRI male mice (8–10 weeks old) were provided. The mice were classified into five groups. Iron dextran was administered as i.p. injection (100 mg/kg/day) four times a week for four subsequent weeks. The treated groups received 30 and 60 mg/kg/day naringin for a month. After histological processing, the brain sections were stained with Perls’ stain kit for iron spots, and Congo red was used to stain the brain and hippocampus for amyloid-beta plaques. 30 mg/kg/day of naringin was shown to decrease nonheme iron in an efficient manner; iron content in this group decreased to 16.83 ± 0.57 μg/g wet weight, a quantity as low as that observed in the normal saline-receiving group. The nonheme iron content in the mice receiving 60 mg/kg/day of naringin was 20.73 ± 0.65 μg/g wet weight. In addition, Aβ plaque numbers in CA1, CA3, and DG areas of the hippocampus decreased significantly following treatment with 30 or 60 mg/kg/day naringin. Naringin has a strong iron chelation capacity and is able to reduce the formation of amyloid plaques. So it can be useful for neuroprotection and prevention of Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

Naringin Chelates Excessive Iron and Prevents the Formation of Amyloid-Beta Plaques in the Hippocampus of Iron-Overloaded Mice

2021

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“…Note: In plaques, mainly Copper (Cu), Zinc (Zn) but also Iron (Fe) are found at high levels. Because the molecular interactions of Fe and Aβ and their biological relevance are still unclear with only very scarce reports on a possible Fe(II) binding to Aβ, [32][33][34] Fe will not be discussed here. The interested readers can find insights into the putative roles of Fe in AD, in the following recent reports (refs.…”

Section: X2 Metal Ions Aβ Peptides and Their Interactionsmentioning

confidence: 99%

Chapter 7. Role of Metal Ions in Alzheimer's Disease: Mechanistic Aspects Contributing to Neurotoxicity

Hureau¹

2022

Alzheimer's Disease

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“…All of the structures were visualized using PYMOL Chimera software version 1 [31]. The calculation procedure was almost the same as that in our previous work [32][33][34] with neutralization. Antibodies were separated from SARS-CoV-2 S-RBD into individual files for docking simulation.…”

Section: Construction Of the Computational Modelmentioning

confidence: 99%

Structural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America

Quinonez

Vahed

Shahraki

et al. 2021

Viruses

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Background: little is known about the forecasting of new variants of SARS-COV-2 in North America and the interaction of variants with vaccine-derived neutralizing antibodies. Methods: the affinity scores of the spike receptor-binding domain (S-RBD) of B.1.1.7, B. 1.351, B.1.617, and P.1 variants in interaction with the neutralizing antibody (CV30 isolated from a patient), and human angiotensin-converting enzyme 2 (hACE2) receptor were predicted using the template-based computational modeling. From the Nextstrain global database, we identified prevalent mutations of S-RBD of SARS-CoV-2 from December 2019 to April 2021. Pre- and post-vaccination time series forecasting models were developed based on the prediction of neutralizing antibody affinity scores for S-RBD of the variants. Results: the proportion of the B.1.1.7 variant in North America is growing rapidly, but the rate will reduce due to high affinity (~90%) to the neutralizing antibody once herd immunity is reached. Currently, the rates of isolation of B. 1.351, B.1.617, and P.1 variants are slowly increasing in North America. Herd immunity is able to relatively control these variants due to their low affinity (~70%) to the neutralizing antibody. The S-RBD of B.1.617 has a 110% increased affinity score to the human angiotensin-converting enzyme 2 (hACE2) in comparison to the wild-type structure, making it highly infectious. Conclusion: The newly emerged B.1.351, B.1.617, and P.1 variants escape from vaccine-induced neutralizing immunity and continue circulating in North America in post- herd immunity era. Our study strongly suggests that a third dose of vaccine is urgently needed to cover novel variants with affinity scores (equal or less than 70%) to eliminate developing viral mutations and reduce transmission rates.

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The initial stage of structural transformation of Aβ42 peptides from the human and mole rat in the presence of Fe2+ and Fe3+: Related to Alzheimer's disease

Cited by 15 publications

References 35 publications

Naringin Chelates Excessive Iron and Prevents the Formation of Amyloid-Beta Plaques in the Hippocampus of Iron-Overloaded Mice

Naringin Chelates Excessive Iron and Prevents the Formation of Amyloid-Beta Plaques in the Hippocampus of Iron-Overloaded Mice

Chapter 7. Role of Metal Ions in Alzheimer's Disease: Mechanistic Aspects Contributing to Neurotoxicity

Structural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America

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