Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification

Background: The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Aβ aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results: In the present work, we found that intracellular Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion: Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism

La narrativa en las historias de vida de la plataforma digital pone.tv

123 p.il.La convergencia de medios produjo un cambio en la producción de contenidos, así como en el consumo de medios. La multiplicación de canales supone el nacimiento de un nuevo modelo narrativo: la narrativa transmedia. La nueva forma de contar historias hace uso de todos los canales disponibles para hacer llegar al consumidor, partes diferentes de su relato, para que éste las interrelacione. Por lo tanto, se plantean nuevas exigencias para los creadores de contenido. Esta tesis aborda los elementos que componen a la narrativa transmedia, sus características y proceso de implementación. A través del estudio del caso de la plataforma digital pone.tv se muestra de qué manera un producto audiovisual puede ir adquiriendo posibles escenarios de desarrollo transmedia a futuro. The convergence of media produced a change in the production of content, as well as in the consumption of media. The multiplication of channels supposes the birth of a new narrative model: the transmedia narrative. The new way of telling stories makes use of all available channels to reach the consumer, different parts of his story, so that it interrelates them. Therefore, new demands are made for content creators. This thesis addresses the elements that make up the transmedia narrative, its characteristics and implementation process. Through the case study of the digital platform pone.tv shows how an audiovisual product can acquire possible scenarios of transmedia development in the future.Fil: Aldunate, Rebeca. Universidad Católica de Salta. Facultad de Artes y Ciencias; Argentina

Intracellular amyloid formation in muscle cells of Aβ-transgenic <it>Caenorhabditis elegans</it>: determinants and physiological role in copper detoxification

Abstract Background The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Aβ aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results In the present work, we found that intracellular Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism.</p

Peptide multifunctionalized gold nanorods decrease toxicity of beta-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease

The properties of nanometric materials make nanotechnology a promising platform for tackling problems of contemporary medicine. In this work, gold nanorods were synthetized and stabilized with polyethylene glycols and modified with two kinds of peptides. The D1 peptide that recognizes toxic aggregates of A beta, a peptide involved in Alzheimer's disease (AD); and the Angiopep 2 that can be used to deliver nanorods to the mammalian central nervous system. The nanoconjugates were characterized using absorption spectrophotometry, dynamic light scattering, and transmission electron microscopy, among other techniques. We determined that the nanoconjugate does not affect neuronal viability; it penetrates the cells, and decreases aggregation of A beta peptide in vitro. We also showed that when we apply our nanosystem to a Caenorhabditis elegans AD model, the toxicity of aggregated A beta peptide is decreased. This work may contribute to the development of therapies for AD based on metallic nanoparticles.Fondecyt 1130425 11130494 1170929 Fondap 15130011 Proyecto Interno UST Proyecto DI 1609/16R Programa Fondecyt Postdoctoral 3140489 Beca CONICYT Doctorado Nacional 2112061