Click‐ligation of coumarin to polyether polyols for polyurethane foams

A simple strategy for the synthesis and functionalization of polyurethanes is described. Anionic ring‐opening polymerization was combined with ‘click’ chemistry to synthesize polyols with fluorescent properties. This route allows the incorporation of a wide range of functionalities in the polyols with an easy, clean and highly selective process compatible with several types of functional groups. The proposed strategy opens the way to the production, in a cost‐effective way, of ‘smart’ polyurethanes with non‐conventional properties like fire retardancy, antimite properties, antibacterial properties, etc. Alkynyl groups were introduced into the polyol chains by the controlled addition of glycidyl propargyl ether as co‐monomer during a conventional anionic ring‐opening copolymerization with propylene oxide. Subsequently 4‐azidomethyl‐7‐methoxycoumarin molecules were introduced onto the alkynyl‐polyether polyols by copper‐catalysed cycloaddition reactions to produce end‐functionalized polyols. The chemical structure of the novel polyols was characterized using infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography with triple detection and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy. These characterization techniques confirmed the presence of a considerable amount of functional groups in the structure of the polyols. Finally, various fluorescent rigid foams, based on the functionalized polyols, were synthesized. Copyright © 2012 Society of Chemical Industry     

Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins

Microglial interaction with amyloid fibrils in the brains of Alzheimer's and prion disease patients results in the inflammatory activation of these cells. We observed that primary microglial cultures and the THP-1 monocytic cell line are stimulated by fibrillar beta-amyloid and prion peptides to activate identical tyrosine kinase-dependent inflammatory signal transduction cascades. The tyrosine kinases Lyn and Syk are activated by the fibrillar peptides and initiate a signaling cascade resulting in a transient release of intracellular calcium that results in the activation of classical PKC and the recently described calcium-sensitive tyrosine kinase PYK2. Activation of the MAP kinases ERK1 and ERK2 follows as a subsequent downstream signaling event. We demonstrate that PYK2 is positioned downstream of Lyn, Syk, and PKC. PKC is a necessary intermediate required for ERK activation. Importantly, the signaling response elicited by beta-amyloid and prion fibrils leads to the production of neurotoxic products. We have demonstrated in a tissue culture model that conditioned media from beta-amyloid- and prion-stimulated microglia or from THP-1 monocytes are neurotoxic to mouse cortical neurons. This toxicity can be ameliorated by treating THP-1 cells with specific enzyme inhibitors that target various components of the signal transduction pathway linked to the inflammatory responses.