Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials

Recent studies suggest that the toxicity of familial amyotrophic lateral sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective recruitment to mitochondria. Here we demonstrate that each of 12 different familial ALS-mutant SOD1s with widely differing biophysical properties are associated with mitochondria of motoneuronal cells to a much greater extent than wild-type SOD1, and that this effect may depend on the oxidation of Cys residues. We demonstrate further that mutant SOD1 proteins associated with the mitochondria tend to form cross-linked oligomers and that their presence causes a shift in the redox state of these organelles and results in impairment of respiratory complexes. The observation that such a diverse set of mutant SOD1 proteins behave so similarly in mitochondria of motoneuronal cells and so differently from wild-type SOD1 suggests that this behavior may explain the toxicity of ALS-mutant SOD1 proteins, which causes motor neurons to die

LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization

The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S) pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S) shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells

Single-step green synthesis and characterization of gold-conjugated polyphenol nanoparticles with antioxidant and biological activities

Background: Gold nanoparticles (GNPs) are likely to provide an attractive platform for combining a variety of biophysicochemical properties into a unified nanodevice with great therapeutic potential. In this study we investigated the capabilities of three different natural polyphenols, epigallocatechin-3-gallate (EGCG), resveratrol (RSV), and fisetin (FS), to allow synergistic chemical reduction of gold salts to GNPs and stabilization in a single-step green process. Moreover, antioxidant properties of the nanosystems, as well as preliminary antiproliferative activity and apoptotic process investigation of model EGCG-GNPs on stable clones of neuroblastoma SH-SY5Y cells expressing CFP-DEVD-YFP reporter, were examined. Methods: The GNPs were characterized by physicochemical techniques, polyphenol content, and in vitro stability. The antioxidant activity of the GNPs was also determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS) radical-scavenging assays. Stable clones of neuronal SH-SY5Y-CFP-DEVD-YFP were generated and characterized, and cell viability after treatment with EGCG-GNPs was assessed after 72 hours through a 3(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Activation of the apoptotic pathways was also investigated by Western blot analysis. Results: With a diameter in the size range of 10–25 nm, the obtained nanoparticles (NPs) were found to contain 2.71%, 3.23%, and 5.47% of EGCG, RSV, and FS, respectively. Nanoprototypes exhibited remarkable in vitro stability in various media, suggesting that NP surface coating with phytochemicals prevents aggregation in different simulated physiological conditions. The scavenging activities for DPPH and ABTS were highly correlated with EGCG, RSV, and FS content. Moreover, high correlation coefficients between the ABTS and DPPH values were found for the prepared nanosystems. EGCG-GNPs induce a dose-dependent reduction on SH-SY5Y-CFP-DEVD-YFP cell viability that is likely to involve the activation of the apoptotic pathways, similarly to free EGCG, as suggested by the processing of the CFP-DEVD-YFP reporter. Conclusion: These results prompted us to propose the ecofriendly synthesized EGCG-, RSV-, and FS-based nanogold conjugates as suitable carriers for bioactive polyphenols to be used for the treatment of disorders associated with oxidative stress, including neurodegenerative disorders, cardiovascular disease, and cancer.</br

Don Quichotte avant Don Quichotte? Les récits de chevalerie du xive au xviesiècle en France, Italie et Espagne: production et réception. Textes édités par Catherine Croizy-Naquet et Michelle Szkilnik

Ce numéro spécial de la revue “Tirant” réunit les actes d’un colloque international qui s’est déroulé à Paris, à l’Université Sorbonne Nouvelle, du 30 mai au 1er juin 2018; la rencontre se proposait de faire le point sur la réception et l’évolution des récits de chevalerie en Espagne, France et Italie entre xive et xvie siècle. Les trois contributions dont nous rendons compte ici font partie de la deuxième section du volume, intitulée Renouveler le récit chevaleresque. Géraldine Toniutti, Imi..

«Cahiers de Recherches Médiévales et Humanistes» 30

La section qui a pour titre Experiments in fiction: framing and reframing romance at the end of the Middle Ages, and beyond du volume 30, 2015 des «CRMH» comprend des articles issus des communications présentées à l’International Congress of the Courtly Literature Society de Lisbonne en 2013. Comme le rappelle Jane H.M. Taylor dans l’Introduction (pp. 287-295), le xve siècle a été en France une période de grande floraison littéraire et d’une importante production codicologique: en analysant d..

Christophe Imperiali, En quête de Perceval. Étude sur un mythe littéraire

Issu d’une thèse de doctorat en Littérature comparée soutenue à Paris-4 en 2008, le présent volume fait le point sur la réception du mythe de Perceval tout au long des huit siècles de son existence littéraire. L’ouvrage est organisé en trois sections. La première partie («Quelques réflexions autour du “mythe littéraire” et de l’usage qui peut en être fait», pp. 13-70), strictement méthodologique et théorique, s’attache à fournir une définition opératoire de la notion de mythe littéraire. Aprè..

Antoine Calvet, Alchimie et philosophie dans la section alchimique du manuscrit français 2872 de la Bibliothèque de l’Arsenal (xve siècle)

Cet article montre l’intérêt du ms. Paris, BnF, Arsenal 2872 (second quart du xve siècle) qui rassemble un corpus de dix textes alchimiques dans lesquels l’art transmutatoire est mis en relation avec deux autres disciplines scientifiques: l’astrologie et, surtout, la médecine. Copie de luxe fabriquée pour un personnage de la haute noblesse dont l’identité est inconnue, ce manuscrit témoigne du charme exercé par l’alchimie sur les milieux princiers de la fin du Moyen Âge. A. Calvet met en lumi..

Naissances. Génération et création, «Questes. Revue pluridisciplinaire d’études médiévales», 27

Nous signalons ici les contributions plus spécialement centrées sur la littérature médiévale, en renvoyant à la section «Quattrocento» pour les autres. Aurélie Houdebert compare les miniatures initiales de deux manuscrits du Cléomadès d’Adenet le Roi (vers 1280). L’un (Arsenal 3142), copié pour un membre de la cour de France peu après la composition du roman, représente la naissance de l’œuvre, en mettant en scène tant l’auteur que la reine Marie de Brabant, commanditaire du roman, et ses pro..