Gut power: Modulation of human amyloid formation by amyloidogenic proteins in the gastrointestinal tract

Increasing evidence suggests that amyloid formation, i.e., self-assembly of proteins and the resulting conformational changes, is linked with the pathogenesis of various neurodegenerative disorders such as Alzheimer’s disease, prion diseases, and Lewy body diseases. Among the factors that accelerate or inhibit oligomerization, we focus here on two non-genetic and common characteristics of many amyloidogenic proteins: metal binding and asparagine deamidation. Both reflect the aging process and occur in most amyloidogenic proteins. All of the amyloidogenic proteins, such as Alzheimer’s β-amyloid protein, prion protein, and α-synuclein, are metal-binding proteins and are involved in the regulation of metal homeostasis. It is widely accepted that these proteins are susceptible to non-enzymatic posttranslational modifications, and many asparagine residues of these proteins are deamidated. Moreover, these two factors can combine because asparagine residues can bind metals. We review the current understanding of these two common properties and their implications in the pathogenesis of these neurodegenerative diseases.

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Kinetics of amyloid formation and membrane interaction with amyloidogenic proteins

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2006.12.014 ◽

2007 ◽

Vol 1768 (8) ◽

pp. 1923-1934 ◽

Cited By ~ 103

Author(s):

Regina M. Murphy

Keyword(s):

Amyloid Formation ◽

Membrane Interaction ◽

Amyloidogenic Proteins ◽

Kinetics Of

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Soluble oligomers are sufficient for transmission of a yeast prion but do not confer phenotype

The Journal of Cell Biology ◽

10.1083/jcb.201307040 ◽

2013 ◽

Vol 203 (2) ◽

pp. 197-204 ◽

Cited By ~ 13

Author(s):

Jennifer E. Dulle ◽

Rachel E. Bouttenot ◽

Lisa A. Underwood ◽

Heather L. True

Keyword(s):

Prion Proteins ◽

Valuable Insight ◽

Amyloid Formation ◽

Functional Requirements ◽

Yeast Prion ◽

Amyloidogenic Proteins ◽

Isolation And Characterization ◽

Prion Transmission ◽

In Cells

Amyloidogenic proteins aggregate through a self-templating mechanism that likely involves oligomeric or prefibrillar intermediates. For disease-associated amyloidogenic proteins, such intermediates have been suggested to be the primary cause of cellular toxicity. However, isolation and characterization of these oligomeric intermediates has proven difficult, sparking controversy over their biological relevance in disease pathology. Here, we describe an oligomeric species of a yeast prion protein in cells that is sufficient for prion transmission and infectivity. These oligomers differ from the classic prion aggregates in that they are soluble and less resistant to SDS. We found that large, SDS-resistant aggregates were required for the prion phenotype but that soluble, more SDS-sensitive oligomers contained all the information necessary to transmit the prion conformation. Thus, we identified distinct functional requirements of two types of prion species for this endogenous epigenetic element. Furthermore, the nontoxic, self-replicating amyloid conformers of yeast prion proteins have again provided valuable insight into the mechanisms of amyloid formation and propagation in cells.

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Near-Wall Aggregation of Amyloidogenic Aβ 1-40 Peptide: Direct Observation by the FRET

Molecules ◽

10.3390/molecules26247590 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7590

Author(s):

Natalia Katina ◽

Alisa Mikhaylina ◽

Nelly Ilina ◽

Irina Eliseeva ◽

Vitalii Balobanov

Keyword(s):

Kinetic Data ◽

Water Glass ◽

Amyloid Fibrils ◽

Liquid Solution ◽

Conformational Transitions ◽

Self Organization ◽

Amyloid Formation ◽

Amyloidogenic Proteins ◽

Protein Molecules ◽

Polypeptide Chains

The formation of amyloid fibrils is one of the variants of the self-organization of polypeptide chains. For the amyloid aggregation, the solution must be oversaturated with proteins. The interface of the liquid (solution) and solid (vessel walls) phases can trigger the adsorption of protein molecules, and the resulting oversaturation can initiate conformational transitions in them. In any laboratory experiment, we cannot exclude the presence of surfaces such as the walls of vessels, cuvettes, etc. However, in many works devoted to the study of amyloid formation, this feature is not considered. In our work, we investigated the behavior of the Aβ 1-40 peptide at the water–glass, water–quartz, and water–plastic interface. We carried out a series of simple experiments and showed that the Aβ 1-40 peptide is actively adsorbed on these surfaces, which leads to a significant interaction and aggregation of peptides. This means that the interface can be the place where the first amyloid nucleus appears. We suggest that this effect may also be one of the reasons for the difficulty of reproducing kinetic data when studying the aggregation of the amyloid of the Aβ 1-40 peptide and other amyloidogenic proteins

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Cross-talk between amyloidogenic proteins in type-2 diabetes and Parkinson’s disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1610371113 ◽

2016 ◽

Vol 113 (44) ◽

pp. 12473-12477 ◽

Cited By ~ 61

Author(s):

Istvan Horvath ◽

Pernilla Wittung-Stafshede

Keyword(s):

Type 2 Diabetes ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cross Reactivity ◽

Amyloid Formation ◽

Islet Amyloid ◽

Amyloid Fibers ◽

Amyloidogenic Proteins

In type-2 diabetes (T2D) and Parkinson’s disease (PD), polypeptide assembly into amyloid fibers plays central roles: in PD, α-synuclein (aS) forms amyloids and in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids. Using a combination of biophysical methods in vitro we have investigated whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can cross-react. Whereas IAPP forms amyloids within minutes, aS takes many hours to assemble into amyloids and pro-IAPP aggregates even slower under the same conditions. We discovered that preformed amyloids of pro-IAPP inhibit, whereas IAPP amyloids promote, aS amyloid formation. Amyloids of aS promote pro-IAPP amyloid formation, whereas they inhibit IAPP amyloid formation. In contrast, mixing of IAPP and aS monomers results in coaggregation that is faster than either protein alone; moreover, pro-IAPP can incorporate aS monomers into its amyloid fibers. From this intricate network of cross-reactivity, it is clear that the presence of IAPP can accelerate aS amyloid formation. This observation may explain why T2D patients are susceptible to developing PD.

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Habitat Association of Klebsiella Species

Infection Control ◽

10.1017/s0195941700062603 ◽

1985 ◽

Vol 6 (2) ◽

pp. 52-58 ◽

Cited By ~ 111

Author(s):

Susan T. Bagley

Keyword(s):

Drinking Water ◽

Gastrointestinal Tract ◽

Surface Waters ◽

Industrial Effluents ◽

Opportunistic Pathogen ◽

Habitat Associations ◽

Habitat Association ◽

Klebsiella Species ◽

Almost All ◽

Polluted Waters

AbstractThe genus Klebsiella is seemingly ubiquitous in terms of its habitat associations. Klebsiella is a common opportunistic pathogen for humans and other animals, as well as being resident or transient flora (particularly in the gastrointestinal tract). Other habitats include sewage, drinking water, soils, surface waters, industrial effluents, and vegetation. Until recently, almost all these Klebsiella have been identified as one species, ie, K. pneumoniae. However, phenotypic and genotypic studies have shown that “K. pneumoniae” actually consists of at least four species, all with distinct characteristics and habitats. General habitat associations of Klebsiella species are as follows: K. pneumoniae—humans, animals, sewage, and polluted waters and soils; K. oxytoca—frequent association with most habitats; K. terrigena— unpolluted surface waters and soils, drinking water, and vegetation; K. planticola—sewage, polluted surface waters, soils, and vegetation; and K. ozaenae/K. rhinoscleromatis—infrequently detected (primarily with humans).

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