1,721,195 research outputs found

    Force: A messenger of axon outgrowth

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    The axon is a sophisticated macromolecular machine composed of interrelated parts that transmit signals like spur gears transfer motion between parallel shafts. The growth cone is a fine sensor that integrates mechanical and chemical cues and transduces these signals through the generation of a traction force that pushes the tip and pulls the axon shaft forward. The axon shaft, in turn, senses this pulling force and transduces this signal in an orchestrated response, coordinating cytoskeleton remodeling and intercalated mass addition to sustain and support the advancing of the tip. Extensive research suggests that the direct application of active force is per se a powerful inducer of axon growth, potentially bypassing the contribution of the growth cone. This review provides a critical perspective on current knowledge of how the force is a messenger of axon growth and its mode of action for controlling navigation, including aspects that remain unclear. It also focuses on novel approaches and tools designed to mechanically manipulate axons, and discusses their implications in terms of potential novel therapies for re-wiring the nervous system

    Recent advances in the use of magnetic nanoparticles to promote neuroregeneration

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    The complexity of the nervous system is one of the major obstacles for implementing effective strategies of neuroregeneration. During the regeneration process a large number of biological events, including axonal growth, spatial organization of different cell types, cell–cell interactions, cell–matrix interactions, need to be re-assembled. This process requires a cascade of sequential events, which are generally orchestrated by growth factors and signaling cues secreted by specific cell types. The structure reconstruction is often governed by cell migration and creation of a cell niche, which provides the required gradients of biochemical and biophysical signals. Based on the understanding of the basic principles governing a nerve regeneration process, there is a great potential to exploit this knowledge to create synthetic tools to promote or accelerate nerve repair. In this context, nanomedicine is offering extraordinary possibilities to cross biological barriers or to mimic specific components of the regeneration process, such as cell manipulation, cell stimulation, cell homing, spatio-temporally controlled delivery of signaling cues, etc. This commentary focuses on novel perspectives offered by magnetic nanoparticles (MNPs) activated by noninvasive magnetic fields for promoting neuroregeneration or re-innervation in pathological conditions such as neurodegenerative diseases or injuries

    Chemically functionalized carbon nanotubes: emerging vectors for cell therapy

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    Carbon nanotubes are widely used for biomedical applications as intracellular transporters of biomolecules, due to their high propensity to cross cell membranes. In this review we summarize the recent advancement in the functionalization of carbon nanotubes, focusing particular attention on the chemistry involved in the preparation of nanovectors for drug delivery systems, and on the physical and chemical properties that affect cellular up-take and biodistribution phenomena

    Superparamagnetic Nanoparticles: A Biodistribution Study Using Xenopus laevis Embryos

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    Various in-vivo biological models have been proposed for studying the interactions of nanomaterials with biological systems. Recently, there has been a significant increase in interest in the use of non-mammalian embryos, such as the frog Xenopus laevis as valid models for research in nanomedicine. In the present work, we demonstrate that X. laevis is a powerful model for the study of the biodistribution of superparamagnetic nanoparticles (SPION), extensively used in biomedical field for cell separation, MRI diagnostics and magnetic drug-targeting. 10 nl of 25 mg/ml of SPIONs (nano-screen MAG/ARA 200 nm, Chemicell) were microinjected. The biodistribution of SPIONs, following cardiac or pronephros injection of anesthetized frog larvae at stage 37, was studied by both in-vivo florescence and by Prussian blue staining of paraffin sections of the larvae after 24, 48, 72 or 96 hours (at 14 °C). The study confirmed that SPIONs diffused from either injection site by blood stream to all larval organs, being still present after 96 hours of injection

    pdzrn3 is required for pronephros morphogenesis in Xenopus laevis

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    Pdzrn3, a multidomain protein with E3-ubiquitin ligase activity, has been reported to play a role in myoblast and osteoblast differentiation and, more recently, in neuronal and endothelial cell development. The expression of the pdzrn3 gene is developmentally regulated in various vertebrate tissues, including muscular, neural and vascular system. Little is known about its expression during kidney development, although genetic polymorphisms and alterations around the human pdzrn3 chromosomal region have been found to be associated with renal cell carcinomas and other kidney diseases. We investigated the pdzrn3 spatio-temporal expression pattern in Xenopus laevis embryos by in situ hybridization. We focused our study on the development of the pronephros, which is the embryonic amphibian kidney, functionally similar to the most primitive nephric structures of human kidney. To explore the role of pdzrn3 during renal morphogenesis, we performed loss-of-function experiments, through antisense morpholino injections and analysed the morphants using specific pronephric markers. Dynamic pdzrn3 expression was observed in embryonic tissues, such as somites, brain, eye, blood islands, heart, liver and pronephros. Loss of function experiments resulted in specific alterations of pronephros development. In particular, at early stages, pdzrn3 depletion was associated with a reduction of the pronephros anlagen and later, with perturbations of the tubulogenesis, including deformation of the proximal tubules. Rescue experiments, in which mRNA of the zebrafish pdzrn3 orthologue was injected together with the morpholino, allowed recovery of the kidney phenotypes. These results underline the importance of pdzrn3 expression for correct nephrogenesis
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