Endogenous plastic composite material in the Alzheimer’s brain

Seidler, Norbert W.; Craig, Heather D.; Squire, Trevor J.

doi:10.1016/j.mehy.2006.02.038

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…In summary, these observations suggest that interfacial areas (air-water and water-sevoflurane) may promote similar conformational constraints in that the increased emission and decreased anisotropy may indicate a less compacted and more mobile conformation or aggregate. We propose that the more disordered sub-interfacial ABP as described in this study supports our previous work on the formation of monolayers of polyacrolein-ABP composites [10,13,14]. Likewise, we think that the more disordered supra-interfacial ABP at the water-sevoflurane interface as presented here also supports our work [12] on the production of neuromelanin at this interface.…”

Section: Discussionsupporting

confidence: 90%

“…The subsequent misfolding and aggregation of ABP remains a research area of considerable interest and mystery. We contend that macrostructures and interfaces may have an organizing effect on ABP conformation and its selfassociation [13,14]. In intact APP, the location and position of the ABP sequence is at the outer leaflet of the axonal surface membrane.…”

Section: Introductionmentioning

confidence: 99%

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Interfacial Effects on the Conformation of Amyloid-Beta Peptide

Seidler

Eklund²

2009

PPL

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We examined the effects of air-water and water-sevoflurane interfaces on conformational properties of amyloid-beta peptide (ABP). Fractions were extracted from sub-interfacial (air-water) and supra-interfacial (water-sevoflurane) layers and compared with aqueous bulk layers using fluorescence properties of ABP provided by a single tyrosine. The observations suggest that interfacial ABP may be more disordered than bulk ABP.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Interfacial Effects on the Conformation of Amyloid-Beta Peptide

Seidler

Eklund²

2009

PPL

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“…Furthermore, ACRO is known to polymerize readily, especially in an acidic environment. Polyacrolein itself has been associated with negative human health outcomes, such as Alzheimer’s disease (Seidler and Yeargans, 2004; Liu et al, 2005; Seidler et al, 2006). Moreover, whatever the form acrolein may be taking in the condensed phase, the acute inflammatory response observed indicates that it is still capable of eliciting a biological effect.…”

Section: Discussionmentioning

confidence: 99%

Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 1: Simple VOCs and model PM

Ebersviller

Lichtveld²,

Sexton³

et al. 2012

Preprint

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This is the first of a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOC), particulate matter (PM), and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of gas-only- and PM-only-biological effects, using cultured human lung cells as model indicators. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects) from cells exposed to chamber air relative to cells exposed to clean air. The exposure systems permit gas-only- or PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure. Our simple experiments in this part of the study were designed to eliminate many competing atmospheric processes to reduce ambiguity in our results. Simple volatile and semi-volatile organic gases that have inherent cellular toxic properties were tested individually for biological effect in the dark (at constant humidity). Airborne mixtures were then created with each compound and PM that has no inherent cellular toxic properties for another cellular exposure. Acrolein and p-tolualdehyde were used as model VOCs and mineral oil aerosol (MOA) was selected as a surrogate for organic-containing PM. MOA is appropriately complex in composition to represent ambient PM, and it exhibits no inherent cellular toxic effects and thus did not contribute any biological detrimental effects on its own. Chemical measurements, combined with the responses of our biological exposures, clearly demonstrate that gas-phase pollutants can modify the composition of PM (and its resulting detrimental effects on lung cells) – even if the gas-phase pollutants are not considered likely to partition to the condensed phase: the VOC-modified-PM showed significantly more damage and inflammation to lung cells than did the original PM. Because gases and PM are transported and deposited differently within the atmosphere and the lungs, these results have significant consequences. For example, current US policies for research and regulation of PM do not recognize this “effect modification” phenomena (NAS, 2004). These results present an unambiguous demonstration that – even in these simple mixtures – physical and thermal interactions alone can cause a modification of the distribution of species among the phases of airborne pollution mixtures and can result in a non-toxic phase becoming toxic due to atmospheric thermal processes only. Subsequent work extends the simple results reported here to systems with photochemical transformations of complex urban mixtures and to systems with diesel exhaust produced by different fuels.

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“…Furthermore, ACRO is known to polymerize readily, especially in an acidic environment. Polyacrolein itself has been associated with negative human health outcomes, such as Alzheimer's disease (Seidler and Yeargans, 2004;Liu et al, 2005;Seidler et al, 2006). Moreover, the acute inflammatory response observed indicates that, whatever form ACRO may be taking in the condensed phase, it is still capable of eliciting a biological effect.…”

Section: How Well Do We Understand the Mechanisms?mentioning

confidence: 99%

Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 1: Simple VOCs and model PM

et al. 2012

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Abstract. This is the first of a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOC), particulate matter (PM), and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of biological effects, using cultured human lung cells as model indicators. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects) from cells exposed to chamber air relative to cells exposed to clean air. The exposure systems permit virtually gas-only- or PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure. Our simple experiments in this part of the study were designed to eliminate many competing atmospheric processes to reduce ambiguity in our results. Simple volatile and semi-volatile organic gases that have inherent cellular toxic properties were tested individually for biological effect in the dark (at constant humidity). Airborne mixtures were then created with each compound to which we added PM that has no inherent cellular toxic properties for another cellular exposure. Acrolein and p-tolualdehyde were used as model VOCs and mineral oil aerosol (MOA) was selected as a surrogate for organic-containing PM. MOA is appropriately complex in composition to represent ambient PM, and exhibits no inherent cellular toxic effects and thus did not contribute any biological detrimental effects on its own. Chemical measurements, combined with the responses of our biological exposures, clearly demonstrate that gas-phase pollutants can modify the composition of PM (and its resulting detrimental effects on lung cells). We observed that, even if the gas-phase pollutants are not considered likely to partition to the condensed phase, the VOC-modified-PM showed significantly more damage and inflammation to lung cells than did the original PM. Because gases and PM are transported and deposited differently within the atmosphere and the lungs, these results have significant consequences for a wide range of people. For example, current US policies for research and regulation of PM do not recognize this "effect modification" phenomena (NAS, 2004). These results present an unambiguous demonstration that – even in these simple mixtures – physical and thermal interactions alone can cause a modification of the distribution of species among the phases of airborne pollution mixtures that can result in a non-toxic phase becoming toxic due to atmospheric thermal processes only. Subsequent work (described in companion papers) extends the simple results reported here to systems with photochemical transformations of complex urban mixtures and to systems with diesel exhaust produced by different fuels.

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Endogenous plastic composite material in the Alzheimer’s brain

Cited by 3 publications

References 23 publications

Interfacial Effects on the Conformation of Amyloid-Beta Peptide

Interfacial Effects on the Conformation of Amyloid-Beta Peptide

Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 1: Simple VOCs and model PM

Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 1: Simple VOCs and model PM

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