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Vieri Failli

Publications and source records attributed to Vieri Failli.

8 recordsLinked to original sources
PubMed2006

The Nogo receptor complex: confining molecules to molecular mechanisms.

Myelin inhibitory ligands of the Nogo-66 receptor (NgR1) limit axon regeneration in the adult CNS. Recent findings have identified additional co-receptors (functional homologues) of the trimeric NgR1 complex, post-translational modifications of the co-receptors within the cell membrane and novel Ca(2+)-dependent cytoplasmic-protein phosphorylation mechanisms. Such unique signalling pathways provide the potential to transduce myelin-derived growth inhibitory signals to the axonal cytoskeleton, and have been areas of intense investigation in recent years. Here, we summarize current understanding of the molecular basis of myelin-derived axon-growth inhibition in the CNS.

Amyloid Precursor Protein Secretases↗
PubMed2006

Experimental strategies to promote spinal cord regeneration--an integrative perspective.

Detailed pathophysiological findings of secondary damage phenomena after spinal cord injury (SCI) as well as the identification of inhibitory and neurotrophic proteins have yielded a plethora of experimental therapeutic approaches. Main targets are (i) to minimize secondary damage progression (neuroprotection), (ii) to foster axon conduction (neurorestoration) and (iii) to supply a permissive environment to promote axonal sprouting (neuroregenerative therapies). Pre-clinical studies have raised hope in functional recovery through the antagonism of growth inhibitors, application of growth factors, cell transplantation, and vaccination strategies. To date, even though based on successful pre-clinical animal studies, results of clinical trials are characterized by dampened effects attributable to difficulties in the study design (patient heterogeneity) and species differences. A combination of complementary therapeutic strategies might be considered pre-requisite for future synergistic approaches. Here, we line out pre-clinical interventions resulting in improved functional neurological outcome after spinal cord injury and track them on their intended way to bedside.

Animals↗
PubMed2004

The slit receptor Rig-1/Robo3 controls midline crossing by hindbrain precerebellar neurons and axons.

During development, precerebellar neurons migrate dorsoventrally from the rhombic lip to the floor plate. Some of these neurons cross the midline while others stop. We have identified a role for the slit receptor Rig-1/Robo3 in directing this process. During their tangential migration, neurons of all major hindbrain precerebellar nuclei express high levels of Rig-1 mRNA. Rig-1 expression is rapidly downregulated as their leading process crosses the floor plate. Interestingly, most precerebellar nuclei do not develop normally in Rig-1-deficient mice, as they fail to cross the midline. In addition, inferior olivary neurons, which normally send axons into the contralateral cerebellum, project ipsilaterally in Rig-1 mutant mice. Similarly, neurons of the lateral reticular nucleus and basilar pons are unable to migrate across the floor plate and instead remain ipsilateral. These results demonstrate that Rig-1 controls the ability of both precerebellar neuron cell bodies and their axons to cross the midline.

Animals↗
PubMed2004

Lhx9 and lhx9alpha: differential biochemical properties and effects on neuronal differentiation.

The Lhx9 LIM-homeodomain transcription factor and its truncated isoform Lhx9alpha are generated by alternative splicing of the Lhx9 gene. Here we investigated the differential functional properties of these two isoforms. Lhx9alpha, which lacks parts of the homeodomain, was unable to bind DNA in EMSA experiments, but was able to associate with CLIM cofactors in GST pull-down assays. In transfection experiments in PC12 cells, Lhx9alpha fusion constructs systematically showed a nuclear localization, as opposed to Lhx9 fusion constructs, which also localized to the cytoplasm. Moreover, Lhx9 increased NGF-induced neuronal differentiation of PC12 cells. Lhx9alpha, on the other hand, did not significantly increase neuronal differentiation but had an effect on the morphology of PC12 cells. Finally, as tested by RT-PCR experiments on transfected PC12 cells, Lhx9 was not able to induce the transcription of Lhx9alpha. Our results show significantly different functional properties for Lhx9 and Lhx9alpha, and suggest that Lhx9alpha can compete away limiting amounts of nuclear CLIM cofactors. Thus, Lhx9 and Lhx9alpha isoforms could be implicated in regulating various aspects of neuronal differentiation.

Animals↗
PubMed2002

Expression of the LIM-homeodomain gene Lmx1a (dreher) during development of the mouse nervous system.

The expression pattern of Lmx1a, a LIM-homeodomain gene disrupted in the dreher mouse neurological mutant, is described during development. Lmx1a is predominantly expressed in the developing nervous system from embryonic day E8.5 to adulthood, in restricted areas. Major expression domains include the dorsal midline (roof plate) of the neural tube, the cortical hem, the otic vesicles, the developing cerebellum and the notochord. The Lmx1a expression pattern is therefore well correlated with the various aspects of the phenotype of the dreher mutant mice.

Animals↗
PubMedDate not supplied

Injury-related dynamic myelin/oligodendrocyte axon-outgrowth inhibition in the central nervous system.

CONTEXT: By contrast with the glial scar, myelin was considered a constitutive static inhibitory barrier unreactive to lesions in the central nervous system (CNS). However, recent results suggest considerable add-on inhibition of myelin as a result of CNS injury. Furthermore, catastrophic events cause morphological and biochemical changes in the axon itself. This results in the accumulation of cytoskeleton components and intraaxonal transported proteins paralleled by extensive membrane remodelling at the axonal tip (a process called axotomy) which might modify the axonal response to its inhibitory environment. STARTING POINT: Ji-Eun Kim and colleagues recently reported an axonal subpopulation with a different capacity to respond to myelin inhibitors (Neuron 2004; 44: 439-51). Axonal specificity but also evidence for injury reactivity summarised here challenges our understanding of axon-growth inhibition in the injured CNS. This might be due to (i) qualitative and quantitative enrichment of the periaxonal environment by myelin/oligodendrocytes, (ii) increased axonal sensitivity to its inhibitory environment, and (iii) axons and lesion-induced, altered axonal signalling. WHERE NEXT? Postlesional reactive inhibition of myelin or the oligodendrocyte necessitates the development of novel screening approaches and therapeutic agents to promote axonal regeneration. Moreover, we need to improve our understanding of the pathophysiology of the lesion to find more efficient experimental strategies to restore neurological function.

Animals↗