Amyloid fibrils: potential food safety implications

Greger, Michael

doi:10.1504/ijfsnph.2008.023011

Cited by 7 publications

(4 citation statements)

References 58 publications

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“…(2007) have provided experimental evidence which reveals that an amyloid-containing food (Foie gras) product can substantially hasten the development of protein amyloidosis in a susceptible mouse population . Further, research reports have also indicated that amyloid deposits present in cattle can also cause amyloidosis in a mouse model. , Considering the results reported by these studies, aspartame consumption seems to be capable of predisposing serious consequences both directly and indirectly. Direct defects can arise from the formation of cytotoxic aspartame fibrils and toxic amyloids of other essential proteins and peptides due to aspartame-driven amyloid cross-seeding.…”

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Although there is no evidence of amyloid fibrils in milk, we have speculated that fibrils may form in certain dairy products. If tested and proved correct, then further research to minimize the fibril content of dairy products may be advisable (Greger, 2008 …”

Section: Discussionmentioning

confidence: 99%

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

Holt

Carver

Ecroyd

et al. 2013

Journal of Dairy Science

394

240

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A typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins. The ability to suppress amyloid fibril formation by forming an alternative amorphous aggregate is also not unique to caseins and underlies the action of molecular chaperones such as the small heat-shock proteins. The open structure of the protein matrix of casein micelles is fragile and easily perturbed by changes in its environment. Perturbations can cause the polypeptide chains to segregate into regions of greater and lesser density. As a result, the reliable determination of the native structure of casein micelles continues to be extremely challenging. The biological functions of caseins, such as their chaperone activity, are determined by their composition and flexible conformation and by how the casein polypeptide chains interact with each other. These same properties determine how caseins behave in the manufacture of many dairy products and how they can be used as functional ingredients in other foods. aBStraCtA typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosp...

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“…Healthy mice exposed orally to AA fibrils did not develop amyloidosis, whereas those additionally receiving a concurrent inflammatory stimulus developed a pronounced disease within days ( 83 ). Conditions associated with elevated SAA levels may include chronic infections, as well as non-infectious chronic inflammatory diseases, and certain tumors ( 84 ). The concentration of SAA can drastically increase at an acute inflammation as a response to cytokines, especially IL-1, IL-6, and TNF-α ( 85 ).…”

Section: Four Good Reasons Why the Commercialization Of Milk From Cow...mentioning

confidence: 99%

Health concerns about possible long-term effects of legally marketed milk and dairy from animals with intramammary infections

Schadt

2023

Front. Public Health

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Milk and dairy from animals with subclinical mastitis infections are marketable. Mastitis is detected with the somatic cell count (SCC). The EU regulation, among the stricter ones, limits an average of 400,000 somatic cells/ml in milk. Other countries have higher or no thresholds. This level suggests 40% of infected animals, and we indeed consume mastitic milk and dairy. A worldwide prevalence of dairy cattle and buffaloes with subclinical mastitis is estimated to range between 34 and 46%. The current food safety regulations account for mastitis pathogens, their toxins, and the risk of antimicrobial residues, but milk from animals with mastitis contains also compounds that derive from an immune response and inflammation process with biological function for the offspring. To the best of the current knowledge, it cannot be excluded that these compounds do not interfere with human homeostasis and that they do not contribute to redox or cytokine dysregulation that, in turn, could promote certain chronic diseases. These compounds include radicals, oxidation products, nitrosamines, and proinflammatory cytokines with nitrosamines being already recognized as probable carcinogens. Mastitis also alters the composition of caseins, plasmin, and plasminogen activators, which may be related to increased transformation into amyloid with similar characteristics as the fibrils associated with Alzheimer's disease. We should determine whether these bioactive compounds could, alone or in combination, represent any long-term risk to the consumer's health. Adapted regulations and concomitant subsidies for farmers are suggested, for sensing tools that reveal individual SCC and mastitis at milking. Frequent SCC determination is the prerequisite for any mastitis control program.

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Amyloid fibrils: potential food safety implications

Cited by 7 publications

References 58 publications

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

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

Invited review: Caseins and the casein micelle: Their biological functions, structures, and behavior in foods

Health concerns about possible long-term effects of legally marketed milk and dairy from animals with intramammary infections

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