Effect of agitation on the peptide fibrillization: Alzheimer's amyloid‐<i>β</i> peptide 1‐42 but not amylin and insulin fibrils can grow under quiescent conditions

Tiiman, Ann; Noormägi, Andra; Friedemann, Merlin; Krishtal, Jekaterina; Palumaa, Peep; Tõugu, Vello

doi:10.1002/psc.2513

Cited by 35 publications

(27 citation statements)

References 26 publications

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“…This observation can be explained due to the use of continuous agitation conditions and the presence of salts. Comparable results described a lag time of 3 min using similar experimental conditions . The progressive increase in ThT fluorescence over 50 h indicates the formation of β‐sheet structures of Aβ 1–42 , sufficient this time for the aggregate formation to be observed.…”

Section: Resultsmentioning

confidence: 64%

“…Comparable results described a lag time of 3 min using similar experimental conditions. [24] The progressive increase in ThT fluorescence over 50 h indicates the formation of β-sheet structures of Aβ 1-42 , sufficient this time for the aggregate formation to be observed. This result was confirmed by TEM images (Figure 2B).…”

Section: Inhibitory Effects Of Indolic Compounds On Aβ 1-42 Aggregationmentioning

confidence: 96%

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In Vitro Effects of Serotonin, Melatonin, and Other Related Indole Compounds on Amyloid‐β Kinetics and Neuroprotection

Hornedo-Ortega

Costa

Cerezo

et al. 2018

Molecular Nutrition Food Res

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Section: Resultsmentioning

confidence: 64%

Section: Inhibitory Effects Of Indolic Compounds On Aβ 1-42 Aggregationmentioning

confidence: 96%

In Vitro Effects of Serotonin, Melatonin, and Other Related Indole Compounds on Amyloid‐β Kinetics and Neuroprotection

Hornedo-Ortega

Costa

Cerezo

et al. 2018

Molecular Nutrition Food Res

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“…Agitation was reported to increase the rate of protein aggregation, including that of bovine and human insulin . It is not clear, however, whether or not agitation affects oligomer formation and the resulting fibrillar morphology.…”

Section: Resultsmentioning

confidence: 99%

“…In our study insulin at neutral pH under quiescent conditions did not aggregate even after prolonged incubation of 65 days. To facilitate aggregation, samples of insulin at neutral pH were agitated by magnetic stirring at a rate of 155 rpm, which is a relatively low rate in comparison to agitation rates used in previous studies . Particularly notable and unexpected was a rapid emergence of large micrometer‐sized aggregates observed by AFM and TEM imaging concomitant with an increased opacity of insulin at neutral pH.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of insulin assembly at acidic and neutral pH: Characterization of low molecular weight oligomers

et al. 2017

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Deficiency in insulin secretion and function that characterize type 2 diabetes often requires administration of extraneous insulin, leading to injection-site amyloidosis. Insulin aggregation at neutral pH is not well understood. Although oligomer formation is believed to play an important role, insulin oligomers have not been fully characterized yet. Here, we elucidate similarities and differences between in vitro insulin aggregation at acidic and neutral pH for a range of insulin concentrations (2.5-100 μM) by using kinetic thioflavin T fluorescence, circular dichroism, atomic force and electron microscopy imaging. Importantly, we characterize the size distribution of insulin oligomers at different assembly stages by the application of covalent cross-linking and gel electrophoresis. Our results show that at the earliest assembly stage, oligomers comprise up to 40% and 70% of soluble insulin at acidic and neutral pH, respectively. While the highest oligomer order increases with insulin concentration at acidic pH, the opposite tendency is observed at neutral pH, where oligomers up to heptamers are formed in 10 μM insulin. These findings suggest that oligomers may be on- and off-pathway assemblies for insulin at acidic and neutral pH, respectively. Agitation, which is required to induce insulin aggregation at neutral pH, is shown to increase fibril formation rate and fibrillar mass both by an order of magnitude. Insulin incubated under agitated conditions at neutral pH rapidly aggregates into large micrometer-sized aggregates, which may be of physiological relevance and provides insight into injection-site amyloidosis and toxic pulmonary aggregates induced by administration of extraneous insulin.

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“…Although human and bacterial amyloids do not share conserved amino acid sequences, numerous features are shared. Bacterial and host amyloid precursor peptides fold into highly conserved beta-sheet structures due to the presence of conversed glutamine and asparagine residues, and amyloids from both origins fibrillize from monomeric subunits (37,132). Both human ␤-amyloid 1-42 and bacterial curli fibrils elicit proinflammatory immune responses generated though TLR2 (88,95,98).…”

Section: Enteric Biofilm Amyloids and Neurodegenerative Diseasesmentioning

confidence: 99%

Curli-Containing Enteric Biofilms Inside and Out: Matrix Composition, Immune Recognition, and Disease Implications

Tursi

Tükel

2018

Microbiol Mol Biol Rev

124

110

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SUMMARYBiofilms of enteric bacteria are highly complex, with multiple components that interact to fortify the biofilm matrix. Within biofilms of enteric bacteria such asEscherichia coliandSalmonellaspecies, the main component of the biofilm is amyloid curli. Other constituents include cellulose, extracellular DNA, O antigen, and various surface proteins, including BapA. Only recently, the roles of these components in the formation of the enteric biofilm individually and in consortium have been evaluated. In addition to enhancing the stability and strength of the matrix, the components of the enteric biofilm influence bacterial virulence and transmission. Most notably, certain components of the matrix are recognized as pathogen-associated molecular patterns. Systemic recognition of enteric biofilms leads to the activation of several proinflammatory innate immune receptors, including the Toll-like receptor 2 (TLR2)/TLR1/CD14 heterocomplex, TLR9, and NLRP3. In the model ofSalmonella entericaserovar Typhimurium, the immune response to curli is site specific. Although a proinflammatory response is generated upon systemic presentation of curli, oral administration of curli ameliorates the damaged intestinal epithelial barrier and reduces the severity of colitis. Furthermore, curli (and extracellular DNA) of enteric biofilms potentiate the autoimmune disease systemic lupus erythematosus (SLE) and promote the fibrillization of the pathogenic amyloid α-synuclein, which is implicated in Parkinson's disease. Homologues of curli-encoding genes are found in four additional bacterial phyla, suggesting that the biomedical implications involved with enteric biofilms are applicable to numerous bacterial species.

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Effect of agitation on the peptide fibrillization: Alzheimer's amyloid‐β peptide 1‐42 but not amylin and insulin fibrils can grow under quiescent conditions

Cited by 35 publications

References 26 publications

In Vitro Effects of Serotonin, Melatonin, and Other Related Indole Compounds on Amyloid‐β Kinetics and Neuroprotection

In Vitro Effects of Serotonin, Melatonin, and Other Related Indole Compounds on Amyloid‐β Kinetics and Neuroprotection

Elucidation of insulin assembly at acidic and neutral pH: Characterization of low molecular weight oligomers

Curli-Containing Enteric Biofilms Inside and Out: Matrix Composition, Immune Recognition, and Disease Implications

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