Renal failure due to primary amyloidosis: a case report and literature review

Mello, Ramon Andrade de; Santos, Dania Sofia Neiva Marques; Freitas-Silva, Margarida; Andrade, Joaquim

doi:10.1590/s1516-31802011000300009

Cited by 2 publications

(1 citation statement)

References 18 publications

(37 reference statements)

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“…Even feeding food products containing amyloid entities has been known to trigger systemic amyloidosis in the subjects . Consumption of aspartame has also been known to predispose nephrotoxic effects, and many studies have also revealed the occurrence of kidney dysfunction due to amyloidosis. − These reports signify the possible relevance of both the amyloidogenic nature and the cross-seeding efficacy of the aspartame molecule to the mechanistic understanding of diverse metabolic disorders related to aspartame consumption.…”

Section: Discussionmentioning

confidence: 99%

Self-Assembly of Artificial Sweetener Aspartame Yields Amyloid-like Cytotoxic Nanostructures

et al. 2019

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Recent reports have revealed the intrinsic propensity of single aromatic metabolites to undergo self-assembly and form nanostructures of amyloid nature. Hence, identifying whether aspartame, a universally consumed artificial sweetener, is inherently aggregation prone becomes an important area of investigation. Although the reports on aspartame-linked side effects describe a multitude of metabolic disorders, the mechanistic understanding of such destructive effects is largely mysterious. Since aromaticity, an aggregation-promoting factor, is intrinsic to aspartame’s chemistry, it is important to know whether aspartame can undergo self-association and if such a property can predispose any cytotoxicity to biological systems. Our study finds that aspartame molecules, under mimicked physiological conditions, undergo a spontaneous self-assembly process yielding regular β-sheet-like cytotoxic nanofibrils of amyloid nature. The resultant aspartame fibrils were found to trigger amyloid cross-seeding and become a toxic aggregation trap for globular proteins, Aβ peptides, and aromatic metabolites that convert native structures to β-sheet-like fibrils. Aspartame fibrils were also found to induce hemolysis, causing DNA damage resulting in both apoptosis and necrosis-mediated cell death. Specific spatial arrangement between aspartame molecules is predicted to form a regular amyloid-like architecture with a sticky exterior that is capable of promoting viable H-bonds, electrostatic interactions, and hydrophobic contacts with biomolecules, leading to the onset of protein aggregation and cell death. Results reveal that the aspartame molecule is inherently amyloidogenic, and the self-assembly of aspartame becomes a toxic trap for proteins and cells, exposing the bitter side of such a ubiquitously used artificial sweetener.

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