The Aβ peptide forms non-amyloid fibrils in the presence of carbon nanotubes

Luo, Jinghui; Wärmländer, Sebastian K.T.S.; Yu, Chien-Hung; Kamran, Muhammad; Gräslund, Astrid; Abrahams, Jan Pieter

doi:10.1039/c4nr00291a

Cited by 47 publications

(58 citation statements)

References 27 publications

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“…Such associations might interfere with, for example, the A␤ self-fibrillation pathway. Our observation of A␤ peptides adsorbing on the surfaces of hydrophobic carbon nanotubes appears to support this hypothesis (94). For A␤, the hydrophobic regions around residues 16 -21 and 29 -35 form the two legs of the A␤ hairpin, which is considered to be the basic unit for A␤ self-aggregation and co-aggregation with other molecules (5).…”

Section: Implications Of A␤ Cross-amyloid Interactionssupporting

confidence: 65%

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Luo

Wärmländer

Gräslund

et al. 2016

Journal of Biological Chemistry

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125

108

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Many protein folding diseases are intimately associated with accumulation of amyloid aggregates. The amyloid materials formed by different proteins/peptides share many structural similarities, despite sometimes large amino acid sequence differences. Some amyloid diseases constitute risk factors for others, and the progression of one amyloid disease may affect the progression of another. These connections are arguably related to amyloid aggregates of one protein being able to directly nucleate amyloid formation of another, different protein: the amyloid cross-interaction. Here, we discuss such cross-interactions between the Alzheimer disease amyloid-␤ (A␤) peptide and other amyloid proteins in the context of what is known from in vitro and in vivo experiments, and of what might be learned from clinical studies. The aim is to clarify potential molecular associations between different amyloid diseases. We argue that the amyloid cascade hypothesis in Alzheimer disease should be expanded to include cross-interactions between A␤ and other amyloid proteins.Alzheimer disease (AD) 3 is the most common form of elderly dementia. Its causes have not yet been clearly elucidated. The two classical AD lesions are depositions of intracellular neurofibrillary tau tangles and extracellular deposits of aggregated amyloid-␤ (A␤) peptides in amyloid plaques in the gray matter of the brain, mainly the hippocampus and neocortex. A␤ is a 36 -43-residue peptide cleaved from the amyloid-␤ protein precursor (A␤PP) by ␥-secretase and ␤-secretase enzymes.Some A␤PP and A␤ mutations increase A␤ production and deposition and/or extend the half-life of A␤ in the brain, but only a fraction (5%) of Alzheimer disease is familial AD (1). Several studies indicate that alterations of the pathologies of other amyloid proteins such as ␣-synuclein (2) and tau (3) are observed in familial AD.The amyloid cascade hypothesis suggests that deposition of A␤ aggregates in brain plays a vital role in AD development (4). The amyloid form of A␤ aggregates is generally defined by in vitro observations: originally by the so-called cross-␤ x-ray diffraction pattern or by observation of fibril structures in microscopy (transmission electron microscopy or atomic force microscopy) (5). Molecular probes recognizing the formation of certain ordered molecular structures include Congo red and thioflavin T, which change their optical properties when bound to amyloid material (5). The terms "on-pathway" and "off-pathway" intermediates are used to differentiate between self-aggregated A␤ species that lead to amyloid formation and those that do not. Missense mutations in the A␤PP, apoE, PS1, and PS2 genes can increase accumulation and toxicity of A␤ aggregates, and the "on-pathway" intermediate aggregates seem to be the most cell-damaging species (6). This provides strong support for the amyloid cascade hypothesis, which nevertheless remains disputed.Although two recent reviews (7, 8) respectively reject and support the amyloid cascade hypothesis, they both agree on one poin...

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Section: Implications Of A␤ Cross-amyloid Interactionssupporting

confidence: 65%

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Luo

Wärmländer

Gräslund

et al. 2016

Journal of Biological Chemistry

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125

108

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“…Lyophilized Aβ(1-40) peptides, with the primary sequence DAEFR5HDSGY10EVHHQ15KLVFF20 AEDVG25SNKGA30IIGLM35VGGVV40, were bought either unlabeled or isotope 13 C, 15 N-labeled from AlexoTech AB (Umeå, Sweden). The Aβ peptides were dissolved to monomeric form as previously described [46], and peptide concentration determined by weight. Mn(II) acetate was purchased from Sigma-Aldrich Co.…”

Section: Methodsmentioning

confidence: 99%

Characterization of Mn(II) ion binding to the amyloid-β peptide in Alzheimer⿿s disease

Wallin

Kulkarni

Abelein

et al. 2016

Journal of Trace Elements in Medicine and Biology

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Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-β (Aβ) peptides. Previous studies have shown that Aβ displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate Aβ aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the Aβ(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to Aβ may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying Aβ binding reveals more complex AD metal chemistry than has been previously considered in the literature.

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“…48,49 This primitive defense mechanism employed by cells to aggregate melanin, [37][38][39][40][48][49][50] a strategy employed to build a scaffold for melanin assembly, forming at least a barrier against pathogens or foreign bodies, 48,49 has been recently associated with oxidative damage and inflammation in several different types of cells. 49 We demonstrate the presence of amyloid in lung, liver, and brain of MWCNT-exposed mice.…”

Section: Discussionmentioning

confidence: 99%

“…36 In this context, data concerning the ability of CNTs to induce protein aggregation and amyloid fiber formation are controversial. [37][38][39][40] The NLRP3 inflammasome, associated with immune responses to CNTs, [27][28][29][30]41 activates release of IL-18, 42 a cytokine associated with amyloid plaque formation in Alzheimer's disease, [43][44][45][46] a neurodegenerative disorder characterized by amyloid accumulation. For these reasons, we investigated the ability of CNTs to induce amyloid production and deposition in vivo, an innate defense mechanism present in most eukaryotic phyla ranging from fungi and invertebrates [47][48][49] to humans.…”

Section: Introductionmentioning

confidence: 99%

Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

Albini¹,

Pagani²,

Pulze³

et al. 2015

IJN

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Carbon nanotubes (CNTs) have been extensively investigated and employed for industrial use because of their peculiar physical properties, which make them ideal for many industrial applications. However, rapid growth of CNT employment raises concerns about the potential risks and toxicities for public health, environment, and workers associated with the manufacture and use of these new materials. Here we investigate the main routes of entry following environmental exposure to multi-wall CNTs (MWCNTs; currently the most widely used in industry). We developed a novel murine model that could represent a surrogate of a workplace exposure to MWCNTs. We traced the localization of MWCNTs and their possible role in inducing an innate immune response, inflammation, macrophage recruitment, and inflammatory conditions. Following environmental exposure of CD1 mice, we observed that MWCNTs rapidly enter and disseminate in the organism, initially accumulating in lungs and brain and later reaching the liver and kidney via the bloodstream. Since recent experimental studies show that CNTs are associated with the aggregation process of proteins associated with neurodegenerative diseases, we investigated whether MWCNTs are able to induce amyloid fibril production and accumulation. Amyloid deposits in spatial association with macrophages and MWCNT aggregates were found in the brain, liver, lungs, and kidneys of exposed animals. Our data suggest that accumulation of MWCNTs in different organs is associated with inflammation and amyloid accumulation. In the brain, where we observed rapid accumulation and amyloid fibril deposition, exposure to MWCNTs might enhance progression of neurodegenerative and other amyloid-related diseases. Our data highlight the conclusion that, in a novel rodent model of exposure, MWCNTs may induce macrophage recruitment, activation, and amyloid deposition, causing potential damage to several organs.

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The Aβ peptide forms non-amyloid fibrils in the presence of carbon nanotubes

Cited by 47 publications

References 27 publications

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Characterization of Mn(II) ion binding to the amyloid-β peptide in Alzheimer⿿s disease

Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

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